Expandable stent and a method for promoting a natural intracranial angiogenesis process, and use of the expandable stent in the method for promoting a natural intracranial angiogenesis process

ABSTRACT

An expandable stent (1) to enhance the supply of blood to downstream tissue which is being supplied with blood through a diseased intracranial artery (100) with a stenosis (102) formed therein by plaque with a bore (103) therethrough. The expandable stent (1) comprises first and second end portions (3,4) joined by a central portion (5). The central portion (5) is configured in the expanded state of the stent (1) to be located in the bore (103) of the stenosis (102) with the first and second end portions (3,4) abutting non-diseased parts (104,106) of the artery (100) adjacent the proximal and distal ends (105,107) of the stenosis (102) for anchoring the stent (1) in the artery (100). The central portion (5) with the stent (1) in the expanded state is configured to apply a radial outward pressure to the stenosis (102) such that the diameter of the bore (103) of the stenosis (102) is maintained at its current diameter or increased to approximately 50% of the non-diseased parts (104,106) of the artery (100).

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a National Stage of International Application No.PCT/EP2018/080213 filed Nov. 5, 2018, claiming priority based on BritishApplication No. 1718299.9 filed Nov. 3, 2017.

The present invention relates to an expandable stent, and in particular,though not limited to an expandable stent for use in treatingintracranial atherosclerotic disease (ICAD). The stent provides a methodto restore sufficient blood flow to mitigate risks of hypoxia, ischemiaand infarction, while being mechanically controlled to prevent lesionsnow-ploughing. Furthermore the stents of this invention are configuredto perfuse downstream tissue to an oligemic state for promoting naturalintracranial angiogenesis.

The invention also relates to a method for promoting a naturalintracranial angiogenesis process, and further the invention relates touse of the expandable stent in the method for promoting a naturalintracranial angiogenesis process. The invention also relates to amethod for treating intracranial atherosclerotic disease (ICAD). Theinvention also relates to use of the expandable stent in the treatmentof intracranial atherosclerotic disease.

Intracranial atherosclerotic stenosis (ICAS) is a narrowing (stenosis)of an artery, vein, lumen or other blood vessel, hereinafter referred toas vessels, within the brain caused by a build-up of plaque (atheroma)on the internal arterial wall, thereby reducing blood flow to the brain.This can lead to thromboembolic or haemodynamic ischemic stroke, aleading cause worldwide of disability.

Intracranial atherosclerotic stenosis has a particularly high prevalenceamongst certain ethnic groups, the condition being especially prevalentamongst Asians (Lancet Neurol. 2013 Nov.; 12(11): 1106-1114). WithinChinese patient populations, the proportion of ischemic stroke which iscaused by ICAS can be as high as 50%.

During the early stages of atherosclerosis, fatty material collectsalong the walls of vessels. The fatty material then thickens, hardenswith calcium deposits, which initially results in narrowing of thevessel, and eventually obstruction of the vessel, thereby preventingblood flow through the vessel.

FIG. 1 illustrates an initial narrowing of a diseased intracranialartery 100. The artery 100 comprises a wall 101. A stenosis 102 isformed by plaque on the wall 101. The stenosis 102 of FIG. 1 has notcompletely blocked the artery 100 but rather has a bore 103 extendingtherethrough. In FIG. 1 the stenosis 102 is of about 90%; that is tosay, about 90% of the healthy diameter of the artery is blocked. Thisrepresents a reduction in open cross-sectional area of the artery by afactor of nearly 100. Symptoms can, however, occur at lower levels ofstenosis. The plaque may eventually block or fully occlude a vessel oran artery or it may develop a rough surface or thrombus that mayrepeatedly generate distal emboli. Other plaque characteristics such asintraplaque haemorrhage/haematoma, lipid rich core, thin fibrous cap canalso result in plaques which are prone to fracture and lead to clotswhich block the vessel or repeatedly generate distal emboli.

The current recommended approach for management of ICAS is to usemedication, such as blood thinning agents, cholesterol-reducingmedications and/or blood-pressure regulating medications. However, therate of ischemic stroke for ICAS patients treated with medication can beas high as 20% at two years (Chimowitz M I, Lynn M J, Howlett-Smith H,et al. Comparison of warfarin and aspirin for symptomatic intracranialarterial stenosis. N Engl J Med 2005; 31:1305-16) (Nahab F, Cotsonis G,Lynnet M, et al. Prevalence and prognosis of coexistent asymptomaticintracranial stenosis. Stroke 2008; 39:1039-41). In the event that anICAS patient has been treated with optimal medication, yet has stillexperienced a second stroke, guidelines allow for further interventions.Currently, the recommended intervention is placement of a stent acrossthe stenosis, performing a balloon angioplasty to open the stenosis, or,more commonly, a combination of both, as a salvage therapy. Stentingacts to widen the stenosis thereby increasing blood flow through thevessel. The stent can also provide a scaffold for a smoother plaquesurface to develop and prevent the recurrent generation of distalemboli. However, some studies have indicated that the use of metalstents risks pushing plaques into adjacent, previously-unaffectedvessels, by a process called “snow-ploughing”. Arterial structures inthe brain are highly branched and a recognised problem with existingstents is the snow-ploughing of material from the stenosis into arterialside branches, or so called “perforator” arteries, thereby blocking themand causing strokes in the territories supplied by these side branches.For this reason, the use of stents and/or balloon angioplasty iscurrently primarily reserved for a follow-up or salvage treatment, oncemedication has failed.

Accordingly, there is a need to provide an alternative approach formanagement of ICAS.

The present invention is directed towards providing an expandable stent,and the invention is also directed towards a method for promoting anatural intracranial angiogenesis process, and further, the invention isdirected towards use of an expandable stent in a method for promoting anatural intracranial angiogenesis process. The invention is alsodirected towards an intracranial vessel comprising the expandable stent.The invention is also directed towards a method for treatingintracranial atherosclerotic disease, and to use of the expandable stentin the treatment of intracranial atherosclerotic disease. Further, theinvention is directed towards the expandable stent for use in treatingintracranial atherosclerotic disease, and to the use of the stent in amethod to restore sufficient blood flow to mitigate risks of hypoxia,ischemia and infarction, while at the same time being mechanicallycontrolled to prevent lesion snow-ploughing. The invention is alsodirected towards a stent, a method and use of the stent to perfusedownstream tissue to an oligemic state for promoting naturalintracranial angiogenesis.

According to the invention there is provided an expandable stent forstenting a stenosis in an intracranial vessel, the stent in its expandedstate being configured to comprise a first end portion having a firstbore extending therethrough, a second end portion spaced apart from thefirst end portion and having a second bore extending therethrough, and acentral portion extending between the first and second end portions andhaving a central bore extending therethrough communicating the first andsecond bores of the first and second end portions with each other, thecentral portion being of external transverse cross-section less than theexternal transverse cross-section of the first and second end portions,wherein the first and second end portions are configured in the expandedstate of the stent to engage an arterial wall of the vessel onrespective opposite ends of the stenosis to anchor the stent in thevessel, and the central portion is configured in the expanded state ofthe stent to extend through a bore extending through the stenosis and tobear on the material forming the stenosis with a radial outward pressureto at least prevent further narrowing of the bore through the stenosis.

The invention also provides an intracranial vessel comprising astenosis, and an expandable stent according to the invention wherein theexpandable stent in its expanded state is located in the vessel with thecentral portion of the stent located in a bore extending through thestenosis and bearing on the material forming the stenosis, and with thefirst and second end portions of the stent engaging a wall of the vesselon respective opposite ends of the stenosis.

Preferably, the first and second end portions of the stent in theexpanded state engage the wall of the vessel adjacent the respectiveopposite ends of the stenosis.

Additionally, the invention provides a method for promoting a naturalintracranial angiogenesis process to supply blood to an intracranialsite being supplied through a vessel having a stenosis therein, themethod comprising:

-   -   providing an expandable stent, the expandable stent comprising a        first end portion having a first bore extending therethrough, a        second end portion spaced apart from the first end portion and        having a second bore extending therethrough, and a central        portion extending between the first and second end portions and        having a central bore extending therethrough communicating the        first and second bores of the first and second end portions with        each other, the central portion being of external transverse        cross-section less than the external transverse cross-section of        the first and second end portions,    -   placing the expandable stent in an unexpanded state in the        stenosis with the central portion of the stent extending through        the bore extending through the stenosis and with the first and        second end portions on opposite ends of the stenosis, and    -   expanding the stent with the first and second end portions of        the expanded stent engaging the wall of the vessel on the        respective opposite ends of the stenosis to anchor the stent in        the vessel, and with the central portion of the expanded stent        bearing on the material forming the stenosis with an outward        radial pressure to at least prevent further narrowing of the        bore extending through the stenosis in order to promote the        natural intracranial angiogenesis process.

Further, the invention provides use of an expandable stent in a methodfor promoting a natural intracranial angiogenesis process to supplyblood to a site being supplied through a vessel having a stenosistherein, the expandable stent comprising a first end portion having afirst bore extending therethrough, a second end portion spaced apartfrom the first end portion and having a second bore extendingtherethrough, and a central portion extending between the first andsecond end portions and having a central bore extending therethrough andcommunicating the first and second end portions with each other, thecentral portion being of external transverse cross-section less than theexternal transverse cross-section of the first and second end portions,wherein the expandable stent in an unexpanded state is placed in thestenosis with the central portion of the stent extending through thebore extending through the stenosis and with the first and second endportions on opposite ends of the stenosis, and the stent is expanded toan expanded state with the first and second end portions of the expandedstent engaging the wall of the vessel on respective opposite ends of thestenosis to anchor the stent in the vessel, and with the central portionof the expanded stent bearing on the material forming the stenosis withan outward radial pressure to at least prevent further narrowing of thebore extending through the stenosis in order to promote the naturalintracranial angiogenesis process.

In one aspect of the invention the central portion is configured in theexpanded state of the stent to bear solely on the material of thestenosis and not on the wall of the vessel.

In another aspect of the invention the first and second end portions areconfigured in the expanded state of the stent to engage the wall of thevessel adjacent the respective opposite ends of the stenosis.

In another aspect of the invention, the first and second end portions inthe expanded state of the stent are of substantially circular transversecross-section.

In a further aspect of the invention the first and second end portionsin the expanded state of the stent are of substantially cylindricalshape.

In another aspect of the invention the first and second end portions areconfigured in the expanded state of the stent to adapt to the shape ofthe adjacent part of the vessel.

In another aspect of the invention the central portion in the expandedstate of the stent is of substantially circular transversecross-section.

In a further aspect of the invention the central portion in the expandedstate of the stent is of substantially cylindrical shape.

In another aspect of the invention the central portion in the expandedstate of the stent is of substantially hourglass shape.

Preferably, the central portion is configured in the expanded state ofthe stent to adapt to the shape of at least a part of the stenosis.

In one aspect of the invention the central portion is configured toexpand to a predefined maximum transverse cross-sectional area in theexpanded state of the stent.

Preferably, the predefined maximum transverse cross-sectional area ofthe central portion is less than the transverse cross-sectional area ofa non-diseased part of the vessel adjacent the stenosis, in order toavoid contact of the central portion with the wall of the vessel.

In one aspect of the invention the external diameters of the first andsecond end portions in the expanded state of the stent do not exceed 5mm.

Preferably, the external diameters of the first and second end portionsin the expanded state of the stent lie in the range of 2 mm to 5 mm.

Advantageously, the external diameters of the first and second endportions in the expanded state of the stent lie in the range of 2.5 mmto 4.5 mm.

In one aspect of the invention the first and second end portions in theexpanded state of the stent are configured to expand to a diameter inthe range of 100% to 125% of the internal diameter of a non-diseasedpart of the vessel adjacent the stenosis.

Preferably the first and second end portions in the expanded state ofthe stent are configured to expand to a diameter in the range of 100% to110% of the internal diameter of a non-diseased part of the vesseladjacent the stenosis.

In another aspect of the invention the maximum external diameter of thestent in the unexpanded state thereof does not exceed 0.6 mm, andpreferably does not exceed 0.5 mm, and advantageously, does not exceed0.4 mm.

Preferably, the maximum external diameter of the stent in the unexpandedstate thereof does not exceed 0.3 mm.

In one aspect of the invention the external diameter of the centralportion in the expanded state of the stent lies in the range of 25% to70% of the external diameters of the first and second end portions.

Preferably, the external diameter of the central portion in the expandedstate of the stent lies in the range of 40% to 75% of the externaldiameters of the first and second end portions.

Advantageously, the external diameter of the central portion in theexpanded state of the stent lies in the range of approximately 50% ofthe external diameters of the first and second end portions.

In one aspect of the invention the external diameters of the first andsecond end portions in the expanded state of the stent are substantiallyequal to each other.

In another aspect of the invention the internal diameter of the centralportion in the expanded state of the stent lies in the range of 25% to70% of the internal diameters of the first and second end portions.

Preferably, the internal diameter of the central portion in the expandedstate of the stent lies in the range of 40% to 75% of the internaldiameters of the first and second end portions.

Advantageously, the internal diameter of the central portion in theexpanded state of the stent lies in the range of approximately 50% ofthe internal diameters of the first and second end portions.

In one aspect of the invention the internal diameters of the first andsecond end portions in the expanded state of the stent are substantiallyequal to each other.

In another aspect of the invention the wall thickness of the stent liesin the range of 0.02 mm to 0.15 mm.

Preferably, the wall thickness of the stent lies in the range of 0.05 mmto 0.1 mm.

In one aspect of the invention the central portion in the expanded stateof the stent is configured to apply a greater radial outward pressure tothe material forming the stenosis than the radial outward pressureapplied by the first and second end portions to the wall of the vessel.

In another aspect of the invention the radial outward pressure appliedby the central portion in the expanded state of the stent is such as tominimise squashing of the material forming the stenosis to therebyminimise urging the material forming the stenosis longitudinally alongthe wall of the vessel.

In a further aspect of the invention the first and second end portionsin the expanded state of the stent are configured to bear on the wall ofthe vessel with a pressure sufficient to prevent the material formingthe stenosis being urged between the corresponding one of the first andsecond end portions and the wall of the vessel.

In another aspect of the invention the central portion in the expandedstate of the stent is configured to bear on the material forming thestenosis with the radial outward pressure to increase the diameter ofthe bore extending through the stenosis to a diameter of at least 25% ofthe non-diseased part of the vessel adjacent the stenosis.

Preferably, the central portion in the expanded state of the stent isconfigured to bear on the material forming the stenosis with the radialoutward pressure to increase the diameter of the bore extending throughthe stenosis to a diameter of at least 30% of the non-diseased part ofthe vessel adjacent the stenosis.

Advantageously, the central portion in the expanded state of the stentis configured to bear on the material forming the stenosis with theradial outward pressure to increase the diameter of the bore extendingthrough the stenosis to a diameter of at least 40% of the non-diseasedpart of the vessel adjacent the stenosis.

Preferably, the central portion in the expanded state of the stent isconfigured to bear on the material forming the stenosis with the radialoutward pressure to increase the diameter of the bore extending throughthe stenosis to a diameter of at least 50% of the non-diseased part ofthe vessel adjacent the stenosis, and may increase the diameter of thebore extending through the stenosis to a diameter of at least 70% andeven 80% of the non-diseased part of the vessel adjacent the stenosis.

Advantageously, the central portion in the expanded state of the stentis configured to bear on the material forming the stenosis with theradial outward pressure to increase the diameter of the bore extendingthrough the stenosis to a diameter in the order of 60% of thenon-diseased part of the vessel adjacent the stenosis.

In one aspect of the invention the central portion terminates at itsopposite ends in respective transition portions, and the central portionis connected to and communicates with the first and second end portionsthrough the transition portions.

In another aspect of the invention at least one of the transitionportions in the expanded state of the stent extends substantiallyperpendicularly to the central portion and to the corresponding one ofthe first and second end portions.

In another aspect of the invention the two transition portions in theexpanded state of the stent extend substantially perpendicularly to thecentral portion and to the corresponding one of the first and second endportions.

In a further aspect of the invention at least one of the transitionportions in the expanded state of the stent is of frusto-conical shape.

Preferably, the two transition portions in the expanded state of thestent are of frusto-conical shape.

In one aspect of the invention the frusto-conical portion of eachtransition portion in the expanded state of the stent defines a coneangle in the range of 30° to 160°.

Preferably, the frusto-conical portion of each transition portion in theexpanded state of the stent defines a cone angle in the range of 30° to110°.

Advantageously, the frusto-conical portion of each transition portion inthe expanded state of the stent defines a cone angle in the range of 60°to 110°.

In one aspect of the invention the transition portions in the expandedstate of the stent are configured to engage the material forming thestenosis adjacent the respective opposite ends thereof.

Preferably, the first and second end portions and the central portionare of one of cage like construction, braided construction andperforated construction defining interstices therein.

In another aspect of the invention the interstices in the centralportion in the expanded state of the stent are of smaller area than theinterstices in the first and second end portions.

Preferably, the interstices in the central portion in the expanded stateof the stent are of sufficiently small area to one of minimise andprevent the material forming the stenosis passing therethrough.Advantageously, the interstices in the transition portions in theexpanded state of the stent are of smaller area than the area of theinterstices in the first and second end portions.

In another aspect of the invention the interstices in the transitionportions in the expanded state of the stent are of sufficiently smallarea to one of minimise and prevent the material forming the stenosispassing therethrough.

In one embodiment of the invention the central portion of the stentdefines a longitudinally extending main central axis, the first endportion defines a longitudinally extending first central axis, and thesecond end portion defines a longitudinally extending second centralaxis.

In another embodiment of the invention the main central axis, the firstcentral axis and the second central axis coincide with each other.

In another aspect of the invention the main central axis is offset fromthe first and second central axes.

In a further aspect of the invention the first and second central axescoincide with each other.

In another aspect of the invention the main central axis extendsparallel to the first and second central axes.

In a further aspect of the invention the main central axis extends at anangle greater than 0° to the first and second central axes.

In one aspect of the invention the stent is configured to expand atblood temperature of a human or animal subject.

In another aspect of the invention a biocompatible film is provided onthe surface of the stent.

In a further aspect of the invention the biocompatible film is implantedwith a medication to prevent further growth of atherosclerotic plaque.

In another aspect of the invention the stent is implanted at a molecularlevel or coated with one of a medication to reduce the thromboticpotential of the stent and a material to promote angiogenesis.

In one aspect of the invention the stent is coated with atherapeutically active material. Preferably, the therapeutically activematerial comprises an angiogenesis promoting material.

-   -   Advantageously, the angiogenesis promoting material comprises        methacrylic acid-co-isodecyl acrylate (MAA-co-IDA; 40% MAA).

In another aspect of the invention the stent is configured to minimiseendothelial shear stress resulting from the stent.

Preferably, the stent is configured so that the endothelial shear stressresulting from the stent does not exceed 250 Pa.

In one aspect of the invention the stent comprises a biocompatiblematerial.

In another aspect of the invention the stent comprises a biocompatiblebiodegradable material.

In a further aspect of the invention the stent comprises a polymermaterial.

In another aspect of the invention the stent comprises a self-expandingmaterial.

In a further aspect of the invention the stent comprises a memorymaterial.

In another aspect of the invention the stent comprises an alloy selectedfrom one or more of the following metals:

-   -   Nickel, titanium, cobalt, stainless steel.

In a further aspect of the invention the stent comprises anon-self-expanding material.

In one aspect of the invention the first and second end portions in theexpanded state of the stent engage the wall of the vessel adjacent therespective opposite ends of the stenosis.

In another aspect of the invention the first and second end portions inthe expanded state of the stent are of substantially circular transversecross-section.

In a further aspect of the invention the first and second end portionsin the expanded state of the stent are of substantially cylindricalshape.

In another aspect of the invention the first and second end portions inthe expanded state of the stent adapt to the shape of the adjacent partof the vessel.

In one aspect of the invention the stent is expanded to the extent thatthe central portion increases the diameter of the bore extending throughthe stenosis to an extent to increase the rate of the blood flow flowingthrough the stenosis to lie in the range of 25% to 80% of the normalblood flow rate through the vessel without the stenosis.

In another aspect of the invention the stent is expanded to the extentthat the central portion increases the diameter of the bore extendingthrough the stenosis to an extent to increase the rate of the blood flowflowing through the stenosis to lie in the range of 30% to 70% of thenormal blood flow rate through the vessel without the stenosis.

In a further aspect of the invention the stent is expanded to the extentthat the central portion increases the diameter of the bore extendingthrough the stenosis to an extent to increase the rate of the blood flowflowing through the stenosis to lie in the range of 40% to 60% of thenormal blood flow rate through the vessel without the stenosis.

Preferably, the stent is expanded to the extent that the central portionincreases the diameter of the bore extending through the stenosis to anextent to increase the rate of the blood flow flowing through thestenosis to lie in the range of approximately 50% of the normal bloodflow rate through the vessel without the stenosis.

Further the invention provides a method of treating intracranialatherosclerosis disease in a subject, the method comprising the steps ofscaffolding the lesion to control migration of atherosclerotic material,dilating the bore of the lesion such that downstream tissue ismaintained in an oligemic state, and preferably, the method comprisesmedicating the patient to promote the development of collateral vesselsto support said oligemic tissue.

Further the invention provides a method for treating a patient that hasan intracranial stenosis, the method comprising the steps of measuringthe length of the stenosis, measuring the diameter of a bore extendingthrough the stenosis, and measuring the diameters of the vessel adjacentthe distal and proximal ends of the stenosis, selecting a stent with acentral portion having a diameter that is at least 50% of the diameterof the vessel adjacent one of the proximal and distal ends of thestenosis, and placing the stent in the vessel with the central portionof the stent extending through the bore of the stenosis, and configuringthe stent to remodel the stenosis to increase the diameter of the boreextending through the stenosis to a diameter preferably of at least 50%of the diameter of the vessel adjacent the proximal end of the stenosis.Preferably, the stent is configured to remodel the stenosis withinthirty days of placing the stent in the vessel.

The invention also provides a method for preventing a secondaryinfarction when treating a stenosis in a vessel of a subject with abranch vessel adjacent the stenosis, the method comprising providing astent that is configured to under perfuse downstream tissue, positioningthe stent relative to the stenosis, and expanding the stent to anhourglass shape to conform to the stenosis, and confirming thepreservation of said branch vessel before implanting the stent.

Further, the invention provides a method for treating a human or animalsubject to restore sufficient blood flow through a vessel in anintracranial vascular system to mitigate the risk of one or more ofhypoxia, ischemia and infarction, the method comprising provided theexpandable stent according to the invention, loading the expandablestent in a collapsed state into a proximal end of a lumen extendingthrough a delivery microcatheter, the distal end of the deliverymicrocatheter being positioned across the stenosis, advancing the stentin the collapsed state through the lumen of the delivery microcatheterand positioning the stent in its collapsed state within the lumen of thedelivery microcatheter adjacent the distal end thereof, such that thecentral portion of the stent in its collapsed is located within the boreof the stenosis. Preferably, the method further comprises withdrawingthe delivery microcatheter while holding the stent with the centralportion thereof located within the bore of the stenosis to expose thesecond end portion of the stent. Preferably, the axial position of thedelivery microcatheter is adjusted along with the axial position of thestent so that one of the first end portion and the second end portion ofthe stent is located in the vessel adjacent a distal end of thestenosis.

Preferably, the method further comprises further withdrawing thedelivery microcatheter to expose the entire stent.

Preferably, the method further comprises expanding the stent to scaffoldthe stenosis.

In one aspect of the invention, the method comprises confirming theposition of the stent by fluoroscopy.

Preferably, the method comprises decoupling the stent from the deliverymicrocatheter or other element of a delivery system.

In another embodiment of the invention, the method comprises capturingan angiographic image of the stent in the stenosis to confirm theposition of the stent.

In another aspect of the invention the method further comprises removingthe delivery catheter from the subject.

In another aspect of the invention the method comprises providing theexpandable stent with a central portion of hourglass shape.

In a further aspect of the invention the expandable stent comprises aradiopaque marker, and preferably, the radiopaque marker is located onone or both of the first end portion and the second end portion of thestent.

In another aspect of the invention the radiopaque markers are locatedadjacent the portion of the central portion of hourglass shape ofminimum diameter.

In another aspect of the invention the method comprises visualizing thestenosis using fluoroscopy and dimensioning key features of the stenosisprior to treatment.

Preferably, the method comprises computing dimensions of the mostsuitable shape of the central portion of the stent of hourglass shapefor the stenosis.

In another aspect of the invention the method comprises positioning thestent in the collapsed state under fluoroscopic guidance, such that thecentral portion of the stent of hourglass shape is located in thestenosis.

Preferably, the stent is expanded with the central portion of hourglassshape located in the stenosis for dilating the bore extending throughthe stenosis to perfuse distal tissue to an oligemic state.

Preferably, the transition portions are configured into an undulatingtubular body.

Advantageously, the first and second end portions, the transitionportions and the central portion are configured into a monolithstructure.

In one embodiment of the invention the transverse cross-sectional areaof the bore through the stenosis is increased by 3080% while the vesseladjacent the stenosis is dilated by less than 18%.

In another embodiment of the invention the transverse cross-sectionalarea of the bore through the stenosis is increased by 2000% while thevessel adjacent the stenosis is dilated by less than 14%.

In another embodiment of the invention the transverse cross-sectionalarea of the bore through the stenosis is increased by 1000% while thevessel adjacent the stenosis is dilated by less than 16%.

In another embodiment of the invention the transverse cross-sectionalarea of the bore through the stenosis is increased by 3000% while thevessel adjacent the stenosis is dilated by less than 12%.

Preferably, the transverse cross-sectional area of the bore through thestenosis is increased in the range of 1000% to 3000% while the vesseladjacent the stenosis is dilated in the range of 10% to 18%.

The advantages of the invention are many. Essentially, the expandablestent according to the invention when located in a stenosis in a vesselwithin the intracranial vascular branched system is not intended tofully reinstate a partially occluded vessel to its fully normal statenor to its original internal diameter, but rather, to maintain bloodflow through the vessel at a partially restricted level, or to increasethe rate of the blood flow through the vessel to a flow rate anywhere inthe range of 25% to 80% of the normal flow rate through that vesselprior to the formation of the stenosis, and preferably, to increase therate of blood flow to approximately 50% of the normal flow rate throughthe vessel prior to the formation of the stenosis. This allowssufficient time to allow natural intracranial angiogenesis within theintracranial vascular system proceed, whereby collateral blood vesselsgrow in order to allow the site or sites being supplied with bloodthrough the diseased vessel to be supplied through one or morealternative vessels which may or may not already supply the site whichis supplied by the diseased vessel. Thus, on completion of the naturalintracranial angiogenesis process the site being supplied by thediseased vessel is fully supplied with a blood supply from the newlygrown collateral vessels resulting from the natural intracranialangiogenesis process.

The stents according to the invention are also configured to treat brainartery lesions that carry significant risk for patients. These lesionshave a high level of restriction (stenosis) and the shear forces of highvelocity blood flowing through these lesions puts the patient at highrisk of a stroke. At the same time intracranial vessels in humansubjects are thinner than in other parts of the body and are thus morefragile than vessels of similar size in the heart or the kidneys orelsewhere. Aggressive stenting in these vessels has been shown to beinferior to medical therapy. In one embodiment this invention providesan entirely new strategy for treating these patients. The method ofpartially dilating these intracranial stenoses with the devices of thisinvention has the effect of restoring sufficient blood flow to ensurethat the downstream tissue is not hypoxic while at the same timepreserving an oligemic state in the vascular bed. This oligemic state inthe intracranial vascular bed promotes the development of collateralvessels (new vessels) in the brain in an angiogenesis process and thistherapeutic strategy allows the brain to evolve its own circulatoryredundancy over time. This has the effect of reducing the risk that thestenosis presents to the patient. Even an acute occlusion at the site ofthe original lesion may not significantly harm the patient in situationwhere collateral vessels have developed.

Another aspect of the expandable stent of this invention is the way inwhich it manages the atherosclerotic material that makes up the body ofthe restriction (stenosis). In a conventional stenting procedure thismaterial is aggressively displaced and it causes the native artery toexpand to accommodate. The expandable stents of this invention avoidthis aggressive action and displace atherosclerotic material to veryminimal levels.

Accordingly, the expandable stent according to the invention, while ingeneral it is used to increase blood flow through the diseased vessel,it is not used to reinstate normal blood flow through the diseasedvessel, since to increase the diameter of the bore extending through thestenosis to reinstate normal blood flow through the diseased vesselwould, in general, result in the material forming the stenosis beingsquashed and spread longitudinally along the vessel wall. Due to thelarge number of branched vessels in the intracranial vascular system andthe closeness of the branches extending from a main vessel or arterythis would result in the material forming the stenosis being spread pastone or more branched vessels adjacent the stenosis thereby blocking thebranched vessels. The squashing and spreading of material forming thestenosis beyond a stent, generally is referred to as “snow-ploughing”.The expandable stent according to the invention and its use avoids thedanger of snow-ploughing, and thus blocking branched vessels or arteriesadjacent to the stenosis, while at the same time maintaining a flow ofblood through the diseased vessel or artery sufficient to promote andsupport the natural intracranial angiogenesis process until it has beencompleted, and new or collateral blood vessels have grown in order toprovide an alternative blood supply to the site or sites supplied by thediseased vessel.

A further advantage of the invention is that by only partly opening thebore through the stenosis, the risk of intracranial hyperperfusioninjury is reduced, and in general avoided. Intracranial hyperperfusioninjury can result from rapid restoration of normal perfusion pressure,and may potentially lead to intracranial haemorrhage. Intracranialhyperperfusion may also involve dysregulation of the intracranialvascular system and hypertension, in the setting of an increase in theintracranial blood flow.

Accordingly, the advantages of the invention are many. Firstly, theexpandable stent avoids snow-ploughing of material forming a stenosiswhich would otherwise block an adjacent branched vessel or branchedvessels adjacent the stenosis. In the neurovascular circulation some ofthese branched vessels are called perforators because they originatefrom vessels that sit in the folds of the brain (ex middle intracranialartery) and they perforate into intracranial tissue of the brain. It isthe case that some of these perforator vessels are associated with veryhigh level functions such as speech and so an occlusion of one of thesetiny vessels can have devastating consequences for the patient. Theexpandable stent of this invention is configured to protect theseperforator vessels from being occluded by snow-ploughing while restoringblood flow to an oligemic level. The expandable stent while avoidingsnow-ploughing of the material forming the stenosis at the same timemaintains, or increases the diameter of the bore extending through thestenosis to an extent that blood flow through the diseased vessel ismaintained at a value of greater than 30% of normal and preferablyapproximately 50% of normal, thereby permitting natural intracranialangiogenesis processes to proceed. The expandable stent according to theinvention maintains the flow of blood at a sufficient flow rate at leastuntil the natural intracranial angiogenesis processes have beencompleted and new or collateral blood vessels have been grown in orderto supply the sites which had originally been supplied by the diseasedvessel or artery. Due to the fact that the blood flow is maintained at avalue of 50% of the normal blood flow rate intracranial hyperperfusionis avoided, and the risk of stroke is also low. Although in some casesthe expandable stent may be configured to increase the flow rate ofblood to 70% of normal, and in some limited cases to 80% of normal.

The invention and its many advantages will be more clearly understoodfrom the following description of some preferred embodiments thereofwhich are given by way of example only with reference to theaccompanying drawings, in which:

FIG. 1 is a cross-sectional side elevational view of a diseaseintracranial artery,

FIG. 2 is a side elevational view of an expandable stent according tothe invention for use in maintaining blood flow through a stenosis inthe diseased artery of FIG. 1 ,

FIG. 3 is an end elevational view of the stent of FIG. 2 ,

FIG. 4 is a cross-sectional side elevational view of the stent of FIG. 2,

FIG. 5 is a cross-sectional side elevational view of the stent of FIG. 2in an unexpanded state,

FIG. 6 is a cross-sectional side elevational view of the stent of FIG. 2in use in the artery of FIG. 1 ,

FIG. 7 is a cross-sectional side elevational view of a delivery systemfor delivering the stent of FIG. 2 into the stenosis of the diseasedartery,

FIG. 8 is a cross-sectional side elevational view of a portion of theartery of FIG. 7 illustrating the stent of FIG. 2 being positioned inthe stenosis of the diseased artery,

FIG. 9 is a view similar to FIG. 8 further illustrating the placing ofthe stent of FIG. 2 in the diseased artery,

FIG. 10 is a side elevational view of an expandable stent according toanother embodiment of the invention,

FIG. 11 is a cross-sectional side elevational view of a stent accordingto another embodiment of the invention,

FIG. 12 is a cross-sectional side elevational view of a stent accordingto a further embodiment of the invention illustrated in a stenosis in adiseased artery,

FIG. 13 is a cross-sectional side elevational view of a stent accordingto a further embodiment of the invention illustrated being placed in astenosis in an artery,

FIGS. 14 a, b and c are side elevational, cross-sectional sideelevational and end elevational views of a stent according to anotherembodiment of the invention,

FIGS. 15 a, b and c are side elevational, cross-sectional sideelevational and end elevational views of a stent according to anotherembodiment of the invention,

FIGS. 16 a, b and c are side elevational, cross-sectional sideelevational and end elevational views of a stent according to anotherembodiment of the invention,

FIGS. 17 a, b and c are side elevational, cross-sectional sideelevational and end elevational views of a stent according to anotherembodiment of the invention, and

FIG. 18 is a perspective view of a stent according to another embodimentof the invention.

Referring to the drawings and initially to FIGS. 2 to 6 thereof, thereis illustrated an expandable stent according to the invention indicatedgenerally by the reference numeral 1. The stent 1 is expandable from anunexpanded state illustrated in FIG. 5 to an expanded state illustratedin FIGS. 2, 3, 4 and 6 . The stent 1 is of dimensions in the unexpandedstate which are suitable for urging the stent through the intracranialvascular system (not shown) in a delivery microcatheter, as will bediscussed below, to a stenosis, for example, the stenosis 102 in anintracranial artery, for example, the diseased intracranial artery 100of the intracranial vascular system (not shown). In the expanded statethe dimensions of the stent 1 are such that the stent 1 expands in thestenosis 102 in order to maintain the bore 103 through the stenosis 102open and/or to increase the transverse cross-sectional area of the bore103 through the stenosis 102 in order to maintain and/or increase therate of blood flow through the stenosis 102. Maintaining or increasingthe rate of blood flow through the stenosis 102 protects downstreamtissue, namely, tissue supplied with blood through the artery 100, fromhypoxia, ischemia and/or infarction while maintaining the downstreamtissue in an oligemic state. This thus promotes a natural intracranialangiogenesis process and allows the natural intracranial angiogenesisprocess to be completed, whereby new collateral blood vessels are grownto supply the downstream tissue which is being supplied through thediseased artery 100. The dimensions of the stent 1 in the expanded stateand the unexpanded state are discussed in more detail below.

The stent 1 in its expanded state comprises a first end portion 3 and asecond end portion 4, both of circular transverse cross-section and ofthe same external and internal diameters. A central portion 5 also ofcircular transverse cross-section extends between the first and secondend portions 3 and 4 and terminates at its opposite ends in respectivetransition portions 7 which connect the central portion 5 to thecorresponding ones of the first and second end portions 3 and 4. In thisembodiment of the invention when the stent 1 is in its expanded statethe transition portions 7 extend substantially perpendicularly from thecentral portion 5, and perpendicularly from the corresponding one of thefirst and second portions 3 and 4. However, as discussed below withreference to FIGS. 11 to 13 , the transition portions 7 may be, forexample, frusto-conical of progressively increasing transversecross-sectional area from the central portion 5 to the first and secondend portions 3 and 4, and indeed in other embodiments of the invention,such stents as the stents described with reference to FIGS. 11 to 13 maybe preferable to the stent 1.

The first and second end portions 3 and 4 are formed by expandable firstand second walls 10 and 11, respectively, having first and second bores12 and 13 extending therethrough. The central portion 5 comprises anexpandable central wall 15 having a bore 16 extending therethroughcommunicating the first and second bores 12 and 13 of the first andsecond end portions 3 and 4, respectively. In this embodiment of theinvention in the expanded state of the stent 1, the first, second, andcentral walls 10, 11 and 15, respectively, are cylindrical. In thisembodiment of the invention the transition portions 7 are formed byrespective transition walls 17, which are expandable, and in theexpanded state of the stent expand outwardly so that the transitionwalls 17 extend perpendicularly from the central wall 15 and from thefirst and second walls 10 and 11. The central wall 15 of the centralportion 5 defines a longitudinally extending main central axis 18, andthe first and second walls 10 and 11 of the first and second endportions 3 and 4 defined respective longitudinally extending first andsecond central axes 21 and 22, respectively. In this embodiment of theinvention the first and second end portions 3 and 4 are axially alignedwith each other, and the central portion 5 is axially aligned with thefirst and second end portions 3 and 4. Accordingly, in this embodimentof the invention the first and second central axes 21 and 22 and themain central axis 18 coincide with each other.

It is envisaged, and indeed will be appreciated by those skilled in theart that the first and second walls 10 and 11 and the central wall 15need not necessarily be cylindrical. For example, it is envisaged thatin the expanded state of the stent 1, the central wall 15 may divergeoutwardly from a central point intermediate the transition walls 17towards the transition walls 17, in other words, the central wall 15 maybe of “hourglass” shape, whereby the diameter of the central wall 15adjacent the transition walls 17 would be greater than the diameter ofthe central wall 15 at the central point midway between the transitionwalls 17, in which case, the diameter of the diverging portions of thecylindrical wall 15 would increase gradually from the central point ofthe central wall 15 towards the transition walls 17. Indeed, it isenvisaged that when the stent 1 is expanded in situ, depending on theshape of the bore 103 extending through the stenosis 102, the centralwall 15 may take up a shape corresponding to the profile of the bore 103extending through the stenosis 102.

It is also envisaged that the first and second walls 10 and 11 of thefirst and second end portions 3 and 4 may be of shape other thancylindrical, and in some embodiments of the invention, it is envisagedthat the first and second walls 10 and 11 in the expanded state of thestent 1 may take up a shape whereby the first and second walls 10 and 11converge in a longitudinal direction from the transition wall 17, or mayconverge from a central point midway between the correspondingtransition wall 17 and a corresponding free end 19 of the end walls 10and 11 towards the corresponding transition wall 17 and thecorresponding free end 19. Indeed, when in situ, it is envisaged thatthe first and second walls 10 and 11 of the first and second endportions 3 and 4 may take up a shape which would correspond to thelongitudinal profile of respective proximal and distal non-diseasedportions 104 and 106, respectively, of the artery adjacent a proximalend 105 and a distal end 107, respectively, of the stenosis 102.

Needless to say, the central wall 15 of the central portion 5 and thefirst and second walls 10 and 11 of the first and second end portions 3and 4 may take up any suitable shape in the expanded state of the stent1 and also when the stent 1 is located in situ in the artery 100, forexample, the external surfaces of the first and second end walls 10 and11 and the central wall 15 may be concave or convex.

It will also be appreciated that in some embodiments of the inventionthe first and second end portions may not be axially aligned with eachother, and furthermore, the central portion 15 may not be axiallyaligned with the first and second end portions 2 and 3. In which case,only the central axes 18, 21 and 22 of those portions of the centralportion 18 and the first and second end portions 3 and 4 which areaxially aligned with each other will coincide. For example, in caseswhere the first and second end portions 3 and 4 are axially aligned, thefirst and second central axes 21 and 22 will coincide with each other,and in cases where the central portion 5 is not axially aligned with thefirst and second end portions 3 and 4, the main central axis 18 of thecentral portion 15 will be offset from the first and second central axes21 and 22 of the first and second end portions 3 and 4. In general, insuch a case, the main central axis 18 would extend parallel to the firstand second central axes 21 and 22 of the first and second end portions 3and 4.

Although, it is envisaged that in some cases the main central axis 18 ofthe central portion 5 may extend at an angle to the first and secondcentral axes 21 and 22 of the first and second end portions 3 and 4.Indeed, in use, depending on the shape and angle of the bore 103extending through the stenosis 102, the central portion 5 may take up anorientation which would extend at an angle to the first and second endportions 3 and 4. In which case, it is envisaged that the first andsecond central axes of the first and second end portions 3 and 4 may notbe axially aligned, but would be offset from each other, and the maincentral axis 18 of the central portion 5 would extend at an angle to thefirst and second central axes 21 and 22 of the first and second endportions 3 and 4. Additionally, in the event of the stenosis 102 beinglocated in a curved or angled artery, the first and second central axes21 and 22 of the first and second end portions 3 and 4 may extend at anangle to each other, and also at respective different angles to the maincentral axis 18 of the central portion 5.

The dimensions of the stent 1 in the expanded state in general, arechosen based on the diameter of the stenosis 102, and the length of thestenosis 102, and also on the diameter of the non-diseased portion ofthe artery 100 adjacent the stenosis 102. In general, the stents 1 willbe provided with the first and second end portions 3 and 4 and thecentral portion 5, as well as the transition portions 7 in a range ofdifferent diameters and lengths in order to accommodate arteries orvessels of different diameters and stenoses of different lengths, andhaving bores extending therethrough of different diameters. Theselection of a stent for a particular stenosis in a particular artery orvessel in general, will be a two-step process. Firstly, a surgeon,interventionist or other surgical or medical personnel would measure thelength of the stenosis, and the diameter of the bore extending throughthe stenosis, as well as the diameter of the non-diseased part 104 and106 of the artery adjacent the respective opposite ends of the stenosis.A stent 1 according to the invention of suitable dimensions would thenbe selected. In the absence of a suitably dimensioned stent 1, a stent 1according to the invention of suitable dimensions would be manufactured.

In this embodiment of the invention the stenosis 102 is formed by plaqueon the arterial wall 101 of the artery 100. The diameter d of a bore 103extending through the stenosis 102 is approximately 0.6 mm.

The length L of the stenosis 102 is approximately 5 mm. The diameter Dof the proximal and distal non-diseased parts 104 and 106, respectively,of the artery 100 adjacent respective proximal and distal ends 105 and107, respectively, of the stenosis 102 is approximately 3 mm.

Accordingly, in this embodiment of the invention the stent 1 isconfigured to expand when placed in situ in the stenosis 102 so that theexternal diameter d₁ of the central portion 5 is approximately 1.5 mmand the external diameters D₁ of the first and second end portions 3 and4 are equal to each other and are approximate 3.5 mm. The axial lengthL₁ of the central portion 5 in the expanded state of the stent 1 isapproximately 5 mm, while the axial length L₂ of the first and secondend portions 3 and 4 in the expanded state of the stent 1 in thisembodiment of the invention are equal to each other and in thisembodiment of the invention are approximately 2 mm. It will beappreciated that the axial lengths of the first and second end portions3 and 4 of the stent 1 may be the same or different.

As mentioned above the dimensions of the stent 1 in the expanded stateare largely dependent on the dimensions of the artery and the stenosisthereof and are chosen to be suitable for the particular stenosis.However, typically, in the expanded state the external diameter d₁ ofthe central portion 5 of the stent 1 would range between 1 mm and 3 mm,and more typically would lie within the range of 1.2 mm to 2.5 mm. Theexternal diameter D₁ of the first and second end portions 3 and 4 of thestent 1 in the expanded state, in general, would lie within the range of2 mm to 5 mm, and more typically would lie in the range of 2.5 mm to 4.5mm. Additionally, the length L₁ of the central portion 5 of the stent 1in the expanded state of the stent would typically lie in the range of 5mm to 20 mm, and more typically, would lie in the range of 5 mm to 15mm. The axial length L₂ of each of the first and second end portions 3and 4 of the stent 1 in the expanded state thereof typically would liein the range of 2 mm to 4 mm, and more typically would lie in the rangeof 2 mm to 3 mm, and may be of the same or different axial lengths.

In order that the stent 1 in the unexpanded state can be manoeuvredthrough the intracranial vascular system to the stenosis 102 in theartery 100, in general, in the unexpanded state, the stent 1 would be ofsubstantially constant external diameter d₃ along its entire axiallength L₃, of not more than 0.6 mm, and the axial length L₃ of the stent1 in the unexpanded state, in general, would not exceed 30 mm, see FIG.5 . Although, depending on the location of the artery or vessel and thestenosis thereof in the intracranial vascular system, the maximumexternal diameter d₃ of the stent 1 in the unexpanded state would notexceed 0.5 mm. Ideally, the stent 1 in the unexpanded state would be ofmaximum external diameter d₃ not exceeding 0.4 mm, and of length L₃ notexceeding 25 mm.

The relationship between the external diameter d₁ of the central portion5 and the external diameter D₁ of the first and second end portions 3and 4 in the expanded state of the stent 1 are chosen so that the radialoutward pressure exerted by the central portion 5 on the stenosis 102 issufficient in order to maintain the diameter of the bore 103 extendingthrough the stenosis 102 to be at least 25% of the diameter of theproximal and distal non-diseased parts 104 and 106 of the artery 100adjacent the proximal and distal ends 105 and 107 of the stenosis 102,and the radial outward pressure exerted by the first and second endportions 3 and 4 on the proximal and distal non-diseased parts 104 and106 of the wall 101 of the artery 100 adjacent the respective proximaland distal ends 105 and 107 of the stenosis 102 is sufficient to anchorthe stent 1 in the artery 100 against the arterial wall 101 thereof. Thepressure exerted by the first and second end portions 3 and 4 on thearterial wall 101 may also be sufficient in many cases to prevent thematerial forming the stenosis 102 being squeezed longitudinally alongthe wall 101 of the artery 100 between the first and second end portions3 and 4 and the wall 101 of the artery 100 from the stenosis 102.

The external diameter d₁ of the central portion 5 of the stent 1 in theexpanded state is chosen to apply a radial outward pressure to thestenosis to increase the diameter of the bore 103 through the stenosis102 to a diameter in the range of 25% to 60%, and in some cases up to75% and even 80% of the diameter of the proximal and distal non-diseasedparts 104 and 106 of the artery 100 adjacent the proximal and distalends 105 and 107, respectively, of the stenosis 102. Although ideally,the external diameter of the central portion 5 in the expanded state issuch as to apply a sufficient radial outward pressure to the stenosis102 to increase the diameter of the bore 103 therethrough toapproximately 50% of the diameter of the proximal and distalnon-diseased parts 104 and 106 of the artery 100 adjacent the proximaland distal ends 105 and 107, respectively, of the stenosis 102.

Additionally, and in general, the external diameter d₁ of the centralportion 5 in the expanded state of the stent 1 is chosen so that theradial outward pressure applied by the central portion 5 of the stent 1in its expanded state to the stenosis 102 is sufficient to increase thediameter of the bore 103 extending through the stenosis 102 to adiameter, such that the blood flow rate through the artery 100 isincreased to a value greater than 50% of the normal blood flow ratethrough the artery prior to the formation of the stenosis. Sinceresistance to flow is inversely related to the fourth power of theinternal diameter of a conduit, the external diameter of the centralportion 5 in the expanded state of the stent 1 is selected based on thisrelationship in order to restore the blood flow rate through the bore103 of the stenosis 102 to 50% or greater than that of the normal bloodflow rate. This, it has been found, is sufficient to maintain the bloodflow to the downstream tissue being supplied by the diseased artery 100to protect the downstream tissue from hypoxia, ischemia and/orinfarction while maintaining the downstream tissue in an oligemic state,and is also sufficient to promote the natural intracranial angiogenesisprocess until it has been completed and new collateral blood vesselshave been grown to supply the sites supplied by the diseased artery.However, in some embodiments of the invention it is envisaged that theexternal diameter of the central portion 5 of the expanded stent 1 maybe such as to lightly bear on the stenosis 102 in order to maintain theblood flow through the artery at the current flow rate or slightly abovethe current flow rate, depending on the current flow rate, which may besufficient to protect the downstream tissue from hypoxia, ischemiaand/or infarction while maintaining the downstream tissue in an oligemicstate.

In general, the radial outward pressure applied to the stenosis 102 bythe central portion 5 is greater than the radial outward pressureapplied by the first and second end portions 3 and 4 to the wall 101adjacent the proximal and distal non-diseased parts 104 and 106 of theartery 100 in the expanded state of the stent 1. However, the centralportion 5 is configured so that the maximum transverse cross-sectionalarea to which the central wall 15 can expand is limited to a predefinedmaximum transverse cross-sectional area, which is chosen to be less thanthe transverse cross-sectional area of the proximal and distalnon-diseased parts 104 and 106 of the artery 100, adjacent the stenosis102. This is to ensure that the central wall 15 of the central portion 5in the expanded state of the stent 1 is spaced apart from the arterialwall 101 of the artery 100, and does not come in contact with thearterial wall 101 of the non-diseased part of the artery 100 adjacentthe stenosis 102.

The stent 1 in this embodiment of the invention is formed from aperforated material which is perforated to form struts 23 suitablyconnected to form interstices 20 therebetween extending through thematerial. In this embodiment of the invention the material of the stent1 comprises a memory metal, so that the stent 1 is self-expanding andpreferably, expands at the normal blood temperature in the human oranimal body. While many metals and other materials may be used toprovide such a self-expanding stent, in this embodiment of the inventionthe material of the stent is a nickel titanium alloy known as Nitinol.In the unexpanded state of the stent 1, the stent 1 is radiallycompressed so that the struts 23 lie adjacent each other, and dependingon the pattern of the perforations which form the stent 1, the struts 23in the compressed unexpanded state of the stent 1 may extend in an axialdirection.

The interstices 20 a extending through the central wall 15 of thecentral portion 5 in the expanded state of the stent 1 are of area lessthan the area of the interstices 20 b extending through the first andsecond walls 10 and 11 of the first and second end portions 3 and 4. Theinterstices 20 c extending through the transition walls 17 of thetransition portions 7 are of area substantially similar to the area ofthe interstices 20 a extending through the central wall 15 of thecentral portion 5. In this embodiment of the invention the interstices20 a and 20 c extending through the central wall 15 of the centralportion 5 and the transition walls 17 of the transition portions 7 inthe expanded state of the stent 1 are of sufficiently small area inorder to at least minimise and preferably prevent the material formingthe stenosis 102 penetrating through the interstices 20 a and 20 c inthe central portion 5 and the transition portions 7. Additionally, byproviding the interstices 20 a and 20 c of the central portion 5 and thetransition portions 7 to be of area smaller than the interstices 20 b ofthe first and second end portions 3 and 4, results in the radial outwardpressure exerted on the stenosis 102 by the central portion 5 beinggreater than the radial outward pressure exerted on the proximal anddistal parts 104 and 106 of the artery 100 by the first and second endportions 3 and 4.

The wall thickness of the first and second walls 10 and 11 of the firstand second end portions 3 and 4 is similar to the wall thickness of thecentral wall 15 of the central portion 5. Accordingly, in the expandedstate of the stent 1 the relationship between the internal diameter d₂of the central wall 15 of the central portion 5 and the internaldiameter D₂ of the first and second walls 10 and 11 of the first andsecond end portions 3 and 4 is substantially similar to the relationshipbetween the external diameter d₁ of the central wall 15 of the centralportion 5 and the external diameter D₁ of the first and second walls 10and 11 of the first and second end portions 3 and 4. In this embodimentof the invention the wall thickness of the first and second end walls 10and 11, the central wall 15 and the transition walls 17 is approximately0.1 mm. However, it is envisaged that the thickness of the first andsecond end walls, the central wall and the transition walls may lie inthe range between 0.02 mm and 0.15 mm, although preferably, thethickness of the first and second end walls, the central wall andtransition walls will ideally lie in the range of 0.05 mm to 0.1 mm. Theselection of the thickness of the first and second end walls, thecentral wall and the transition walls will be chosen to optimise betweenthe strength and function of the stent on the one hand, and minimisingendothelial shear stress resulting from the use of the stent on theother hand. In general, the wall thickness of the stent will be selectedso that the endothelial shear stress does not exceed 250 Pa.

In this embodiment of the invention the stent is configured so that inthe expanded state of the stent the external diameter of the first andsecond end portions 3 and 4 of the stent is approximately 110% of thediameter of the proximal and distal non-diseased parts 104 and 106 ofthe artery adjacent the proximal and distal ends 105 and 107,respectively, of the stenosis 102. However, it is envisaged that theexternal diameter of the first and second end portions 3 and 4 of thestent 1 may be configured to expand in the expanded state of the stentto a diameter lying in the range of 100% to 125% of the diameter of theproximal and distal non-diseased parts 104 and 106 of the arteryadjacent the proximal and distal ends 105 and 107, respectively, of thestenosis 102, and preferably, in the range of 100% to 110% of thediameter of the artery in the proximal and distal non-diseased parts 104and 106 thereof.

The stent 1 is coated with a therapeutically active material, and inthis embodiment of the invention is coated with two therapeuticallyactive materials, one of which comprises an angiogenesis promotingmaterial, and the other of which prevents further growth of plaque.Typically, the angiogenesis promoting material comprises methacrylicacid-co-isodecyl acrylate (MAA-co-IDA; 40% MAA). The therapeuticallyactive material for preventing further growth of plaque may comprise anyone or more of the sirolimus and paclitaxel.

Referring now to FIGS. 7 to 9 there is illustrated a delivery system 30for delivering the stent 1 to the stenosis 102 in the artery 100. Thedelivery system 30 comprises a delivery microcatheter 31 extendingbetween a proximal end 32 and a distal end 33. An elongated bore 34extends through the delivery microcatheter 31 from the proximal end 32to the distal end 33 for accommodating delivery of the stent 1therethrough to the stenosis 102 when the distal end 33 of the deliverymicrocatheter 31 is located in the stenosis 102 and projects distallyfrom the stenosis, see FIG. 7 . The bore 34 is of diameter such that thestent 1 in its unexpanded state is freely slideable through the bore 34,and will vary depending on the diameter of the stent in the unexpandedstate, and typically will be in the range of 0.68 mm to 0.84 mm. Theouter diameter of the delivery microcatheter 31 is such that thedelivery microcatheter 31 is urgeable through the intracranial vascularsystem to and through the bore 103 of the stenosis 102 from a suitableentry point, which typically, may be the femoral, radial, brachial orcarotid arteries. Additionally, the delivery microcatheter 31 is ofsufficient flexibility in order to facilitate negotiating the deliverymicrocatheter 31 through the intracranial vascular system to thestenosis 102 in the artery 100.

An elongated positioning member 40 of diameter less than the diameter ofthe bore 34 of the delivery microcatheter 31 is provided for deliveringthe stent 1 through the delivery bore 34 of the delivery microcatheter31 to the stenosis 102 in the artery 100. The positioning member 40extends between a proximal end 41 and a distal end 42 and terminates atits distal end 42 in a releasable coupling mechanism 44 for releasablycoupling the positioning member 40 to the stent 1 adjacent the free end19 of the first wall 10 of the first end portion 3. The first endportion 3 of the stent 1 is configured for locating in the proximalnon-diseased part 104 of the artery 100 adjacent a proximal end 105 ofthe stenosis 102, while the second end portion 4 is configured forlocating in the distal non-diseased part 106 of the artery 100 adjacenta distal end 107 of the stenosis 102. In this embodiment of theinvention the coupling mechanism 44 for coupling the free end 19 of thefirst wall 10 of the first end portion 3 to the positioning member 40 isa conventional coupling mechanism, which will be known to those skilledin the art, and is operable from the proximal end 41 of the positionmember 40 for releasing the stent 1 from the positioning member 40 whenthe stent 1 has been correctly positioned in the stenosis 102.Alternatively, the coupling mechanism may be releasably coupled to thefree end 19 of the second end wall 11 of the second end portion 4.

In use, typically, the procedure for delivering the stent 1 to thestenosis 102 in the artery 100, commences with a guide wire (not shown)being entered into the intracranial vascular system, typically, throughthe femoral, radial, brachial or carotid arteries. The guide wire isurged from the entry point into the intracranial vascular system, and isurged through the intracranial vascular system to the stenosis 102 inthe artery 100. The guide wire is urged through the bore 103 in thestenosis 102 so that a distal end of the guide wire extends into theartery 100 distally of the distal end 107 of the stenosis 102. Thedelivery microcatheter 31 is then urged over the guide wire through theintracranial vascular system until the distal end 33 of the deliverymicrocatheter 31 extends through the bore 103 extending through thestenosis 102 to the distal non-diseased part 106 of the artery 100adjacent the distal end 107 of the stenosis 102. The guide wire is thenwithdrawn through the bore 34 of the delivery microcatheter 31.

The stent 1 in its unexpanded state is coupled to the positioning member40 adjacent the distal end 42 by the coupling mechanism 44. With thestent 1 in its unexpanded state coupled to the distal end 42 of thepositioning member 40, the positioning member 40 urges the stent 1 intothe bore 34 of the delivery microcatheter 31 adjacent the proximal end32 thereof with the second end portion 4 leading the stent 1. The stent1 is then urged through the bore 34 of the delivery microcatheter 31 tothe distal end 33 thereof by the positioning member 40. When the stent 1is within the bore 34 of the delivery microcatheter 31 adjacent thedistal end 33 thereof, the leading portion of the stent 1, namely, thesecond end wall 10 of the second end portion 4 is exposed by slightlywithdrawing the delivery microcatheter 31 proximally. The second endwall 11 of the second end portion 4 of the stent 1 on being exposed andcoming in contact with the blood at the normal body temperature of thesubject commences to expand in the distal non-diseased part 106 of theartery adjacent the distal end 107 of the stenosis 102, see FIG. 8 .

The position of the stent 1 is adjusted by appropriately maneuvering thedelivery microcatheter 31 and the positioning member 40 simultaneouslyin order to correctly position the second wall 11 of the second endportion 4 in its correct position in the distal non-diseased part 106 ofthe artery 100 adjacent the distal end 107 of the stenosis 102. Once thesecond wall 11 of the second end portion 4 is correctly positioned inthe distal non-diseased part 106 of the artery 100 adjacent the distalend 107 of the stenosis 102, the delivery microcatheter 31 is furtherproximally withdrawn in order to completely expose the stent 1.

The remainder of the stent 1 on coming in contact with the blood in theartery 100 at body temperature expands with the central wall 15 of thecentral portion 5 located in the bore 103 of the stenosis 102 bearing onthe stenosis 102, and the first wall 10 of the first end portion 3bearing on the proximal non-diseased part 104 of the artery 100 adjacentthe proximal end 105 of the stenosis 102. The material forming thestenosis 102 is completely contained within an annulus 108 defined bythe central wall 15 of the central portion 5, the transition walls 17 ofthe transition portions 7 and the portion of the wall 101 of the artery100 adjacent the stenosis 102.

The positioning member 40 is decoupled from the stent 1 by decouplingthe coupling mechanism 44 from the stent 1. The positioning member 40and the delivery microcatheter 31 are withdrawn through the intracranialvascular system and in turn through the femoral, radial, brachial orcarotid arteries as the case may be.

With the stent 1 in its expanded state in the stenosis 102 the materialforming the stenosis 102 is retained in the annulus 108 by the centralwall 15 of the central portion 5 and the transition walls 17 of thetransition portions 7 and by the action of the first and second walls 10and 11 of the first and second end portions 3 and 4 bearing on theproximal and distal non-diseased parts 104 and 106 of the artery 100adjacent the proximal and distal ends 105 and 107 of the stenosis 102.The action of the first and second walls 10 and 11 of the first andsecond end portions 3 and 4 on the proximal and distal non-diseasedparts 104 and 106 retain the stent 1 firmly anchored in the artery 100,and also prevent the material forming the stenosis 102 being urgedbetween the wall 101 of the artery 100 and the first and second walls 10and 11 of the first and second end portions 3 and 4. The central wall 15of the central portion 5 bears on the stenosis 102 to either maintainthe diameter of the bore 103 extending through the stenosis 102 at itsdiameter prior to placing the stent 1 in the stenosis 102, or toincrease the diameter of the bore 103 extending through the stenosis 102to a diameter sufficient to maintain the flow rate of blood through theartery 100 at or greater than 50% of the normal flow rate of the bloodtherethrough prior to the formation of the stenosis 102 therein. Bymaintaining the flow rate of the blood through the artery 100 at orgreater than 50% of the normal flow rate, the downstream tissue isprotected from hypoxia, ischemia and infarction while maintaining thedownstream tissue oligemic state. Thus, the natural intracranialangiogenesis process is promoted whereby new and collateral bloodvessels are grown to provide a blood supply to the downstream tissuesupplied by the diseased artery 100.

The provision of the therapeutically active intracranial angiogenesismaterial coated onto the stent further enhances the natural intracranialangiogenesis process, and the therapeutically active material coatedonto the stent for preventing further growth of plaque, prevents or atleast minimises any further growth of plaque.

Referring now to FIG. 10 there is illustrated a stent according toanother embodiment of the invention indicated generally by the referencenumeral 50. The stent 50 is substantially similar to the stent 1, andsimilar components are identified by the same reference numerals. Thestent 50 in this embodiment of the invention is also particularlysuitable for stenting a intracranial artery, such as the artery 100having a stenosis 102 therein, for maintaining or increasing the rate ofblood flow through the stenosis 102 to protect downstream tissue fromhypoxia, ischemia and/or infarction while maintaining the downstreamtissue in an oligemic state, for in turn promoting natural intracranialangiogenesis. The dimensions of the stent 50 are within the dimensionalranges discussed with reference to the stent 1. The main differencebetween the stent 50 and the stent 1 lies in the transition portions 7.In this embodiment of the invention instead of the transition portions 7being formed by a transition wall 17 extending perpendicularly from thecentral wall 15 of the central portion 5 and extending perpendicularlyfrom the first and second walls 10 and 11 of the first and second endportions 3 and 4, the transition portions 7 of the stent 50 are formedby frusto-conical wall portions 52, which in turn are formed bytransition walls 53 which diverge outwardly from the central wall 15 ofthe central portion 5 to the first and second walls 10 and 11 of thefirst and second end portions 3 and 4, respectively.

The wall thickness of the transition walls 53 is substantially similarto the wall thickness of the first and second walls 10 and 11 and thecentral wall 15 of the first and second end portions 3 and 4 and thecentral portion 5, respectively. The external diameter of the transitionwalls 53 adjacent the central wall 15 of the central portion 5 issimilar to the external diameter d₁ of the central wall 15. The internaldiameter of the transition walls 53 adjacent the central wall 15 of thecentral portion 5 is similar to the internal diameter d₂ of the centralwall 15 of the central portion 5. The external diameter of thetransition walls 53 adjacent the first and second walls 10 and 11 of thefirst and second end portions 3 and 4 is similar to the externaldiameter D₁ of the first and second walls 10 and 11 of the first andsecond end portions 3 and 4, while the internal diameter of thetransition walls 53 adjacent the first and second walls 10 and 11 of thefirst and second end portions 3 and 4 is similar to the internaldiameter D₂ of the first and second walls 10 and 11 of the first andsecond end portion 3 and 4.

In this embodiment of the invention the cone angle defined by thefrusto-conical transition walls 53 is approximately 60°. This, thus,results in the external diameter of each transition wall 53 increasingfrom the central wall 15 to the corresponding one of the first andsecond walls 10 and 11 at a rate of approximately 1.72 mm per 1 mm oflength from the central wall 15.

In this embodiment of the invention the stent 50 also comprises a memoryalloy know as Nitinol, and is formed of perforated construction havinginterstices 20. The interstices 20 a and 20 c extending through thecentral wall 15 and the transition walls 53 are of area less than thearea of the interstices 20 b extending through the first and secondwalls 10 and 11 of the stent 50. In this embodiment of the invention thearea of the interstices 20 a and 20 c extending through the central wall15 and the transition walls 53 is such as to minimise, and in general,prevent the material forming the stenosis 102 penetrating through thecentral wall 15 and the transition walls 53.

In this embodiment of the invention the stent 50 is also coated with atherapeutically active intracranial angiogenesis promoting material, anda therapeutically active material for preventing the growth of plaque.

Use of the stent 50 and the delivery of the stent 50 to the stenosis 102of the artery 100 is similar to that already described with reference tothe use and delivery of the stent 1 to the stenosis 102 of the artery100. However, in this embodiment of the invention when the stent 50 hasbeen urged through the bore 34 of the delivery microcatheter 31 by thepositioning member 40, the delivery microcatheter 31 is urged proximallyto expose both the second end wall 11 and the adjacent transition wall53 thereby permitting the second wall 11 and the adjacent transitionwall 53 to expand on coming into contact with the blood in the artery100 of the subject, so that the second wall 11 of the stent 50 engagesand bears on the distal non-diseased part 106 of the artery 100 distallyof the stenosis 102. However, thereafter the maneuvering of the deliverymicrocatheter 31 and the positioning member 40 to accurately positionthe stent 50 in the stenosis 102 is similar to that described withreference to delivery and positioning of the stent 1.

Referring now to FIG. 11 there is illustrated a stent according toanother embodiment of the invention indicated generally by the referencenumeral 60. The stent 60 is substantially similar to the stent 1, andsimilar components are identified by the same reference numerals. Thestent 60 in this embodiment of the invention is also particularlysuitable for stenting a intracranial artery, such as the intracranialartery 100 having a stenosis 102 therein for maintaining or increasingthe rate of blood flow through the stenosis 102 to protect downstreamtissue from hypoxia, ischemia and/or infarction while maintaining thedownstream tissue in an oligemic state, for in turn promoting naturalintracranial angiogenesis. The dimensions of the stent 60 are within thedimensional ranges discussed with reference to the stent 1. The onlydifference between the stent 60 and the stent 1, is that in the stent60, the central portion 5 is of “hourglass” shape having a minimumexternal diameter d₁. Transition portions 7 extending from the centralportion 3 are of frusto-conical shape, similar to the transitionportions 7 of the stent 50. In this embodiment of the invention the areaof the interstices 20 a and 20 c of the central portion 5 and thetransition portions 7 are of area smaller than the area of theinterstices 20 b of the first and second end portions 3 and 4.Additionally, in this embodiment of the invention the area of theinterstices 20 a and 20 c of the central portion 5 and the transitionportions 7 is such as to at least minimise, and preferably, preventmaterial forming the stenosis 102 extending through the interstices 20 aand 20 c in the central portion 5 and the transition portions 7.

Otherwise the stent 60 and its use is substantially similar to thatdescribed with reference to the stent 1, and is of dimensions within theranges discussed in connection with the stent 1.

Referring now to FIG. 12 there is illustrated a stent according to afurther embodiment of the invention indicated generally by the referencenumeral 70. The stent 70 is substantially similar to the stent 1, andsimilar components are identified by the same reference numerals. Thestent 70 in this embodiment of the invention is also particularlysuitable for stenting a diseased artery, for example, the artery 100having a stenosis 102 therein, for maintaining or increasing the rate ofblood flow through the stenosis 102 to protect downstream tissue fromhypoxia, ischemia and/or infarction while maintaining the downstreamtissue in an oligemic state, for in turn promoting natural angiogenesis.The diameter dimensions of the stent 70 are within the diameterdimensional ranges discussed with reference to the stent 1. However, inthis case a perforator artery 109 is branched off from the artery 100 ata location adjacent the stenosis 102. In this embodiment of theinvention the length L₁ of the stent 70 between the first and second endportions 3 and 4, including the central portion 5 and the transitionportions 7 is of sufficient length so that the first and second endportions 3 and 4 engage the proximal and distal non-diseased parts 104and 106 of the artery such that both the stenosis 102 and the connectionof the perforator artery 109 are contained within the annulus 108defined between the central portion 5, the transition portions 7 and thewall 101 of the artery 100 adjacent the stenosis 102.

In this embodiment of the invention the radial outward pressure exertedby the central portion 5 on the stenosis 102 is such as to maintain therate of the blood flow through the artery 100 at approximately 50% ofthe normal blood flow rate through the artery 100 prior to the formationof the stenosis 102. However, the radial outward pressure exerted by thecentral portion 5 on the stenosis 102 is such as to prevent excessivesquashing of the material forming the stenosis 102 between the centralportion 5 and the arterial wall 101 to the extent that the material ofthe stenosis would extend longitudinally along the arterial wall 101,and would have resulted in blocking of the perforator artery 109. Inthis embodiment of the invention while the area of the interstices 20 aof the central portion 5 and the interstices 20 c of the transitionportions 7 is such as to prevent material forming the stenosis 102extending therethrough, the area of the interstices 20 a and 20 cextending through the central portion 5 and the transition portions 7 issuch as to permit blood flow through the central portion 5 and thetransition portions 7 to the perforator artery 109.

Referring now to FIG. 13 there is illustrated a stent according toanother embodiment of the invention indicated generally by the referencenumeral 80, which is also suitable for urging through an intracranialvascular system to a stenosis 102 in an intracranial artery 100 in orderto maintain the diameter or to increase the diameter of the bore 103through the stenosis 102 for maintaining or increasing the rate of bloodflow through the stenosis 102 to protect downstream tissue from hypoxia,ischemia and/or infarction while maintaining the downstream tissue in anoligemic state, for in turn promoting and supporting a naturalintracranial angiogenesis process. In this embodiment of the inventionthe stent 80 is not of a self-expanding material, and accordingly, isconfigured for delivery to the stenosis 102 by a balloon microcatheter82. The balloon microcatheter 82 comprises an elongated microcatheter 83terminating at its distal end 84 in a balloon 85. The balloon 85 isappropriately shaped so that when inflated it inflates to take up theapproximate shape of the stenosis 102 and the proximal and distalnon-diseased parts 104 and 106 of the artery 100. The stent 80 whenexpanded by the balloon 85 in the stenosis 102 is configured to take upa shape substantially similar to that of the stent 50, whereby the stent80 when expanded by the balloon 85 comprises first and second endportions 3 and 4, a central portion 5 of diameter less than the diameterof the first and second end portions 3 and 4, and respectivefrusto-conical transition portions 7 extending from the central portion5 to the first and second end portions 3 and 4. The material of thestent 80, is such that once expanded by the balloon 85 in the stenosis102, the stent 80 retains its expanded shape, thereby maintaining thebore 103 extending through the stenosis 102 at a diameter in order toprovide a blood flow rate through the stenosis 102 of approximately 50%of the normal flow rate through the artery 100 prior to the formation ofthe stenosis 102. The material of the stent is of perforatedconstruction having interstices 20 extending through the first andsecond end portions 3 and 4, the central portion 5 and the transitionportions 7. The interstices 20 a and 20 c extending through the centralportion 5 and the transition portions 7 are smaller than the intersticesextending through the first and second end portions 3 and 4, as alreadydescribed with reference to the stent 1.

Delivery of the stent 80 to the stenosis 102 is substantially similar tothe delivery of the stent 1 to the stenosis 102 as already describedwith reference to FIGS. 7 to 9 , with the exception that instead ofdelivering the stent 80 through the delivery microcatheter 31 by apositioning member 40, the stent 1 in the unexpanded state is deliveredthrough the delivery microcatheter 31 on the balloon microcatheter 82.The stent 80 in its unexpanded state is located on the balloon 85 in itsdeflated state, and is delivered through the delivery microcatheter 31to the stenosis 102. On the balloon 85 with the stent 80 thereon in itsunexpanded state being located in the stenosis 102, the balloon 85 isinflated to in turn expand the stent 80 in the stenosis 102, with thecentral portion 5 of the stent 80 bearing on the stenosis 102, and thefirst and second end portions 3 and 4 of the stent 80 bearing on andengaging the proximal and distal non-diseased parts 104 and 106 of theartery 100. On completion of the positioning of the stent 80 in thestenosis 102, the balloon 85 is deflated and withdrawn along with thedelivery microcatheter as already described with reference to FIGS. 7 to9 .

Referring now to FIGS. 14 a, b and c to FIGS. 17 a, b and c , there isillustrated four expandable stents according to further embodiments ofthe invention indicated generally by the reference numerals 90 to 93,respectively, for use in a human or animal subject, for opening, or atleast maintaining a stenosis open in a diseased artery in theintracranial vascular system, for maintaining or increasing the rate ofblood flow through the stenosis 102 to protect downstream tissue fromhypoxia, ischemia and/or infarction while maintaining the downstreamtissue in an oligemic state, for in turn promoting a naturalintracranial angiogenesis process. The expandable stents 90 to 93 aresubstantially similar to the expandable stent 1 described with referenceto FIGS. 2 to 6 , and similar components are identified by the samereference numerals. The main difference between the stents 90 to 93 andthe stent 1 is that, in the expanded state of each of the stents 90 to93 the central portion 5 of each of the stents 90 to 93 is eccentricallylocated relative to the first and second end portions 3 and 4 thereof.In other words, a main central axis 95 defined by the central portion 5of each stent 90 to 93 is offset from first and second central axes 96and 97 defined by the first and second end portions 3 and 4 of thecorresponding one of the stents 90 to 93. In this embodiment of theinvention the first and second end portions 3 and 4 of the stents 90 to93 are axially aligned with each other, and therefore the first andsecond central axes 96 and 97 coincide with each other. However the maincentral axis 95 of the central portion 5 of each stent 90 to 93 extendsparallel to the first and second central axes 96 and 97 of the first andsecond end portions 3 and 4 of the corresponding one of the stents 90 to93, and is transversely offset from the first and second central axes 96and 97 thereof. Although, it is envisaged that the main central axis 95of the central portion 5 in some cases may extend at an angle relativeto the first and second central axes 96 and 97 of the first and secondend portions 3 and 4 of the corresponding stent 90 to 93. The stents 90to 93 are particularly suitable for use in a diseased intracranialartery in which the stenosis is located asymmetrically in the diseasedartery.

In the stents 90 and 91, the transition portions 7 extendperpendicularly from the central portion 5 and also extendperpendicularly from the first and second end portions 3 and 4. In thestents 92 and 93, the transition portions 7 are formed by transitionwalls 17, which are of asymmetric frusto-conical shape. Additionally, inthe stents 90 and 92 of FIGS. 14 a, b and c , and 16 a, b and c,respectively, the central wall 15 of the central portion 5 and the firstand second end walls 10 and 11 of each of the stents 90 and 92 runtangentially to each other along one side of the stent.

The dimensions of the stents 90 to 93 lie within ranges similar to thedimensional ranges discussed with reference to the stent 1 describedwith reference to FIGS. 2 to 6 . Additionally, the stents 90 to 93 mayor may not be coated with a therapeutically active material as describedwith reference to the stent 1.

Use and delivery of the stents 90 to 93 to a stenosis in theintracranial vascular system is similar to that already described withreference to the stent 1 with reference to FIGS. 2 to 9 . Otherwise, thestents 90 to 93, their use and delivery are similar to the stent 1.

Referring now to FIG. 18 there is illustrated a stent according toanother embodiment of the invention indicated generally by the referencenumeral 200 which is also suitable for advancement through a deliverymicrocatheter placed in the intracranial vascular system to a stenosissimilar to the stenosis 102 in an intracranial artery similar to theintracranial artery 100 in order to achieve a threshold level ofdilation to the bore 103 through the stenosis 102 to maintain blood flowthrough the stenosis 102 in order to prevent hypoxia, ischemia ofinfarction and to promote and support a natural intracranialangiogenesis process. The stent 200 is substantially similar to thestent 1, with the exception that the transition portions 7 are formed byfrusto-conical portions, and for convenience similar components to thoseof the components of the stent 1 are identified by the same referencenumerals. In FIG. 18 the stent 200 is illustrated with a support elementextending through the stent 200. The support element does not form apart of the stent 200.

In this embodiment of the invention the stent 200 is of a self-expandingstent made from a nitinol material comprising struts 23 connected atcrowns 201 which define interstices 20 therebetween, the stent 200comprises a highly polished surface finish. It will be noted withreference to FIG. 18 that the stent comprises a first portion 3, asecond portion 4 and a central portion 5 similar to the embodimentsdescribed with reference to the stents of 1, 50, 60, 70 and 80. In thisembodiment the stent 200 comprises transition portions which are offrusto-conical shape defining a cone angle of approximately 110°. Thecrowns 201 comprise V or U shaped elements in the stent pattern and thestruts 23 interconnect the crowns 201.

The stent 200 further comprises a plurality of ring structures, in thisembodiment of the invention seven ring structures. Each ring structurecomprises a plurality of interconnected struts 23 and crowns 201organised to form a tubular ring around the main and first and secondcentral axes 18, 21 and 22, which in this embodiment of the inventioncoincide. Adjacent rings are connected together with connectors. In oneembodiment the connectors are configured such that adjacent rings arespaced apart from each other. In another embodiment the crowns 201 of afirst ring interpenetrate with the crowns 201 of an adjacent ring.

The stent 200 has an expanded state and a collapsed state. In the fullyexpanded state the stent 200 is stress free. The stent 200 iscompressed, and thus stressed, in order for it to assume the collapsedstate for delivery. In the expanded state the V angle θ of the crowns201 is large and in the collapsed state the V angle θ of the crowns 201is small. Indeed the V angle θ of the crowns 201 is less than 5° in thecollapsed state. In contrast the V angle θ of the crowns 201 isrelatively larger in the expanded state. Preferably the V angle θ isgreater than 40° in the expanded state. More preferably the V angle θ isgreater than 60° and even more preferably the V angle θ is greater than80°.

The stent 200 of this embodiment is designed to be conformable and toprotect flow to perforators and branch vessels, such as the perforatorvessel 109 in FIG. 12 . The larger V angle in the expanded configurationis configured to be large to provide flow orifices formed by theinterstices 20 between the struts 23. The struts 23 are configured to beshort and narrow. Short and narrow struts while challenging tomanufacture make the stent 200 more conformable and the narrow struts 23maintain flow through the flow orifices formed by the interstices 20. Inone embodiment the struts 23 are configured such that the length of atleast one ring in the stent is less than 2 mm. In another embodiment thestruts 23 are configured such that the length of at least one ring inthe stent is less than 1.5 mm. In yet another embodiment the struts 23are configured such that the length of at least one ring in the stent isless than 1.0 mm. In one embodiment the struts 23 are configured to beless than 80 micrometres wide. In another embodiment the struts 23 areconfigured to be less than 60 micrometres wide. In yet anotherembodiment the struts 23 are configured to be less than 40 micrometreswide.

In one embodiment at least one ring of the stent structure comprises sixstruts 23 with three pairs of opposing crowns 201. In another embodimentat least one ring of the stent structure comprises eight struts 23 withfour pairs of opposing crowns 201. In another embodiment at least onering of the stent structure comprises ten struts 23 with five pairs ofopposing crowns 201. In another embodiment at least one ring of thestent structure comprises twelve struts 23 with six pairs of opposingcrowns 201. In another embodiment at least one ring of the stentstructure comprises fourteen struts 23 with seven pairs of opposingcrowns 201. In another embodiment at least one ring of the stentstructure comprises sixteen struts 23 with eight pairs of opposingcrowns 201. In the embodiment of the stent 200 illustrated in FIG. 18 atleast one ring of the stent structure comprises eighteen struts 23 withnine pairs of opposing crowns 201. In one embodiment the number ofstruts in a first ring is greater than the number of struts in anadjacent ring. In one embodiment the number of struts in a first ring isequal to the number of struts in an adjacent ring. In one embodiment thelength of a first ring is greater than the length of a second adjacentring.

The stent 200 of FIG. 18 is shape set to create an undulating tubularstructure with a waisted section, namely, the central portion 5. In oneembodiment the stent is cut from a nitinol tube using a laser process,deburred and grit blasted. The shape setting of the stent 200 comprisesheating the stent to a temperature in excess of 400° centigrade for anumber of minutes until the desired shape is programmed into the stent200. The stent is cooled and the stent is electropolished to produce asurface with a highly polished finish.

In one embodiment the stent comprises a completely connected structure.In such an embodiment every crown of the stent is connected to anadjacent crown either directly or indirectly. The exception to thisinterconnectivity are those crowns that define the very distal and thevery proximal ends of the stent. These crowns are not connected toadjacent crowns.

In another embodiment the stent 200 is configured for visualisation onfluoroscopy. In this embodiment a highly radiopaque metal isincorporated into the structure. The incorporation of the radiopaquemetal allows the interventionalist to visualise the distal end of thestent which may be the first end portion 3 or the second end portion 4,the proximal end of the stent, which is the other one of the first andsecond end portions 3 or 4, the central portion 5 and the transitionportions 7 between the central portion 5 and the first end portion 3 andsecond end portion 4.

In one embodiment the radiopaque element comprises gold, platinum,tantalum or tungsten. In another embodiment the incorporation of theradiopaque element comprises an alloy of Nitinol and the radiopaqueelement. In another embodiment the incorporation of the radiopaqueelement comprises the inclusion of a radiopaque marker into thestructure of the stent. In one embodiment the radiopaque markercomprises a cylindrical slug of a radiopaque metal pressed into aplurality of laser drilled holes in the structure of the stent. Suitableradiopaque metals for use in said cylindrical slug include gold,platinum, tantalum, tungsten or alloys containing a substantial portionof one or more of these elements.

In one embodiment the central portion 5 of the stent 200 is configuredto dilate the bore 103 of the stenosis 102 significantly withoutinducing a corresponding dilation in the vessel wall 100 in the regionof the stenosis 102. The following examples of embodiments of stentssimilar to the stent 200 but of various dimensions and placed instenoses 102 of various dimensions highlight this advantage of theinvention.

EXAMPLE 1

Inputs

Internal diameter D of the vessel 100 3 mm External diameter d₁ of thecentral portion 5 of the 1.4 mm stent 200 External transversecross-sectional area of the vessel 7.07 mm² 100 adjacent the stenosis102 External transverse cross-sectional area of the central 1.54 mm²portion 5 of the stent 200 Diameter d of the bore 103 extending throughthe stenosis 0.25 mm 102 Transverse cross-sectional area of the bore 103extending 0.046 mm² through the stenosis 102 % occlusion by the stenosis102 92%

Calculations

Increase in transverse cross-sectional area of the bore 3036%  103extending through the stenosis 102 Transverse cross-sectional area ofthe stenosis annulus 1.490 mm² formed by the displaced material of thestenosis Diameter of the dilated vessel adjacent the stenosis 3.30 mmIncrease in the vessel diameter adjacent the stenosis 10%

Conclusion

With a 92% stenosis the stent 200 of this example can increase the crosssectional area of the bore of the stenosis by over 3000%, while onlydilating the vessel diameter by 10%.

EXAMPLE 2

Inputs

Internal diameter D of the vessel 100 2.5 mm External diameter d₁ of thecentral portion 5 of the 1.2 mm stent 200 External transversecross-sectional area of the vessel 4.91 mm² 100 adjacent the stenosis102 External transverse cross-sectional area of the central 1.13 mm²portion 5 of the stent 200 Diameter d of the bore 103 extending throughthe stenosis 0.3 mm 102 Transverse cross-sectional area of the bore 103extending 0.071 mm² through the stenosis 102 % occlusion by the stenosis102 88%

Calculations

Increase in transverse cross-sectional area of the bore 1500%  103extending through the stenosis 102 Transverse cross-sectional area ofthe stenosis annulus 1.060 mm² formed by the displaced material of thestenosis Diameter of the dilated vessel adjacent the stenosis 2.76 mmIncrease in the vessel diameter adjacent the stenosis 10.3%

Conclusion

With an 88% stenosis the stent 200 of this example can increase thecross sectional area of the bore of the stenosis by over 1500%, whileonly dilating the vessel diameter by 10.3%.

EXAMPLE 3

Inputs

Internal diameter D of the vessel 100 2 mm External diameter d₁ of thecentral portion 5 of the 1.1 mm stent 200 External transversecross-sectional area of the vessel 3.14 mm² 100 adjacent the stenosis102 External transverse cross-sectional area of the central 0.95 mm²portion 5 of the stent 200 Diameter d of the bore 103 extending throughthe stenosis 0.5 mm 102 Transverse cross sectional area of the bore 103extending 0.196 mm² through the stenosis 102 % occlusion by the stenosis102 75%

Calculations

Increase in transverse cross-sectional area of the bore 384% 103extending through the stenosis 102 Transverse cross-sectional area ofthe stenosis annulus 0.754 mm² formed by the displaced material of thestenosis Diameter of the dilated vessel adjacent the stenosis 2.23 mmIncrease in the vessel diameter adjacent the stenosis 11.4% 

Conclusion

With a 75% stenosis the stent 200 of this example can increase the crosssectional area of the bore of the stenosis by over 384%, while onlydilating the vessel diameter by 11.4%.

Accordingly, it can be seen from the above three examples that the stent200 according to the invention of different dimensions when used instenoses of different bore diameters can produce a significant increasein the stenosis bore transverse cross-section area for a relativelysmall increase in the diameter of the vessel resulting from the radialoutward action of the central portion 5 of the stent 200 on the materialforming the stenosis. Typically the increase in the transversecross-sectional area of the bore extending through a stenosis can rangefrom 300% to over 3000% for an increase in the diameter of the vesseladjacent the stenosis in the range of 10% to 12%.

In the embodiments of the invention where the stents have not beendescribed as being coated with a therapeutically active material, ingeneral, although not necessarily, but preferably, the stents accordingto the invention will be coated with a therapeutically active material.A preferred therapeutically active material with which the stentsaccording to these embodiments of the invention will be coated is anangiogenesis promoting material. The stents according to the inventionmay be coated with any suitable angiogenesis promoting material, forexample, methacrylic acrylate (MAA-co-IDA; 40% MAA).

While the stents according to the invention have been described ascomprising Nitinol, it is envisaged that the stents may comprise anysuitable biocompatible material, such as stainless steel or cobaltalloy. By providing the stents to be of perforated construction, thequantity of metal in the stents is minimised, which has the advantage ofreducing the thrombotic potential of the stents, and notably permitsflow of blood from the stented artery to a perforator artery through thecentral wall, the transition walls and the first and second walls of thecentral, transition and first and second end portions, respectively, ofthe stent, as described in connection with the stent 80 of FIG. 13 , inthe case of a perforator artery branching from an artery adjacent astenosis. The less material used in the stents, the lower the potentialfor material to encourage formation of thrombosis once implanted in anartery.

While the stents according to the invention have been described ascomprising a memory metal, the stents may be of a non-memory metal, andfurthermore, may be of a non-self-expanding material. For example, it isenvisaged that the stents may be of a material which is anon-self-expanding material as in the case of the stent 80. Furthermore,it will be readily apparent to those skilled in the art that the stent80 may be made of a self-expanding memory material.

While the stents according to the invention have been described forstenting a stenosis in an intracranial artery, the stents according tothe invention may be used for stenting a stenosis in any intracranialvessel, such as a vein, lumen or other such intracranial blood vessel.

In other embodiments of the stents, a biocompatible film or membrane maybe provided to at least one surface of the stents. The film or membranemay or may not be perforated.

The film or membrane may be a non-woven fabric made of plastic fibrils.It is bonded to, or forms a bond with, the walls of the stents. The filmor membrane may also be made into a thin strand which can be woven intoa lattice which is layered onto the stent. The membrane and/or thelattice may be deposited on the stents in a manner that is aligned withthe struts of the stents, or alternatively in a non-aligned manner. Incertain embodiments of the invention, the membrane may have a porousstructure capable of accommodating pharmaceutical materials andreleasing these materials into the surrounding vessels and plaque, underphysiological conditions.

The membrane may optionally be implanted or coated with one or morepharmaceutical compositions or other compositions having a desirableeffect on the properties of the stents. This addresses the challenge ofcoating the stents surfaces with pharmaceutical materials. Thesecompositions can release medication over time into the surroundingtissues, vascular surface or plaques. Proliferation-inhibitingsubstances such as paclitaxel and rapamycin, for example, can bebeneficial. Other examples are substances that prevent thrombosis, orprevent liquid embolic agents or glue from adhering to the membraneand/or the stents.

The film or membrane may be suitably made of a polymeric material, suchas polyurethane, polytetrafluoroethylene, polyester, polyamide orpolyolefin. These polymeric membranes are not easily attached to astent. Conventionally, stent membranes are held mechanically against avessel wall or plaque by the radial force of an expanding stent.However, in the present invention, the central portion of the stents donot contact the arterial wall. The stents according to the inventionhaving a membrane made from a polymeric material which is not easilyattached to the walls of the stent are provided with a suitableconnection of the membrane to the stents, typically a mechanicalconnection. Connections of this type are also useful if the stentsrequire re-sheathing into a microcatheter for adjustment or relocationof the stent to another area.

The membranes of the stents may be conveniently made by spraying ontothe stent walls, provided the stent walls are compatible with thepolymer as regards formation of suitable bonds, or by electrospinning ofthe non-woven fabric around the struts of the stents; by applying anelectric current, the fibrils of the membrane are separated from apolymer solution and deposited on a substrate. The technique ofelectrospinning is well known in the art and will not be described infurther detail here. The deposition causes the fibrils to agglutinateinto a non-woven fabric. It can be formed into strands that can bewoven, if so chosen. The fibrils generally have a diameter of from 100to 1000 nm. Membranes produced by electrospinning are very thin anduniform in thickness and can easily form a bond with the stent walls.Such membranes are strong enough to withstand mechanical stress duringcompression of the stents into a deliverable state, and duringmaneuvering of the stents along and into tortuous vessels. Suchmembranes can be pierced easily, mechanically, as required, withoutcreating an opening that gives rise to fractures or cracks. Thethickness and length of the fibrils can be controlled by theelectrospinning process. Examples of such membranes includepoly(lactide-co-caprolactone) (PLCL) which can have a degradation timeof 6-18 months; poly(caprolactone) (PCL) which can have a degradationtime of 2-3 years; or stiffer materials such as polylactides (PLA),poly(lactide-co-glycosides) (PLGA), polyacrylonitrile (PAN) orpolyurethane (PU).

The membrane can be composed of a single layer or multiple layers.Multiple layers may be produced by different methods, for example afirst layer by electrospinning, a second by spray coating and a third byelectrospinning. Active pharmaceutical or other agents can be implantedon one or several of these layers. The agent can be released bydiffusion or by degradation or erosion of the layers of the membrane.Radiopaque substances may also be implanted in the membrane so that itis more easily visible to the techniques used during stent implantation.In particular, in order to further promote and support angiogenesis, thestent may be coated with methacrylic acid ecoisodecyl acid-co-isodecylacrylate (MAA-co-IDA; 40% MAA) or similar substances known to promoteangiogenesis.

The membrane may be laced with graphene to improve its strength andflexibility. Additionally, or alternatively, the membrane may comprise athin film Nitinol.

The stents may be made of a biodegradable material such that it has alimited lifespan. Polymer-based stents are conventionally based onpoly(L-lactide) (PLLA), chosen because it is able to maintain a radiallystrong scaffold that breaks down over time into lactic acid, a naturallyoccurring molecule that the body can use for metabolism. Other polymersin development include tyrosine polycarbonate and salicylic acid.

While a specific delivery system has been described for delivering thestent 1 to a stenosis in a intracranial artery, other suitable deliverymeans may be used, for example, via a balloon catheter. The stentsaccording to the invention are constructed to be inserted withoutrequiring pre-dilatation of the vessel. However, in certain conditions,pre-dilation of the ICAS may be indicated in order to navigate adelivery microcatheter or balloon microcatheter past the stenotic focus.Similarly, the stents may be constructed so that post-dilatation(dilatation of the stent with a balloon after insertion) is notrequired. However, in certain instances, such as where there is heavilycalcified atherosclerotic plaque, post-dilation may be advantageous.Therefore, the stents, whilst not of themselves requiring pre-dilationor post-dilation, is compatible with pre-dilatation and post-dilatation.Where the stent is not self-expanding, a further aspect of the inventionis the provision of a shaped dilation balloon, which will cause theouter ends of the stent to be dilated to a greater extent than the innersection, so as to achieve a dilated stent shape with dimensions aspreviously described for the self-expanding stent, as described withreference to FIGS. 2 to 12 and 14 to 18 .

The stents according to the invention have been described as comprisingperforated expandable walls, such that they may be folded-up in theunexpanded state to form a low profile for delivery into the arterialsystem. A low profile configuration allows for delivery into the smallerintracranial vessels and arteries via smaller microcatheters. Theconfiguration of the stents can be of an open, closed or woven stentdesign. The structure of the stents is illustrated as a closed celltype. The cell construction of the stents cause the stent to beauto-expandable once inserted into an artery. The stents according tothe invention assumes a dumbbell shape upon expansion.

The stents may be formed with a reattachment system so that they may bere-sheathed even when fully delivered, such that an operator mayre-adjust the deployment until fully satisfied with the positioning ofthe stents, relative to the stenosis. Conventional electrolyticseverance of an intravascular stent implant involves using anelectrolytically corrodible structure on the end of a delivery wire atthe connection between the delivery wire and the intravascular stentimplant. Such a device can make use of the voltage applied to theintravascular implant serving as an anode for electro-thrombosis.Alternatively, a mechanical reattachment system may be employed.

Accurate deployment of stents may be obtained via appropriatelypositioned radio-opaque markers which are visible under x-rayfluoroscopy, as is known in the art. Optionally, markers may be providedat the proximal and distal ends of the central portion of the stents.Alternatively or additionally, the central portion of stents may be mademore radio-opaque by the application of a gold coating to the struts ofthe stents. Likewise, the whole of the stents can be substantiallycoated with a radio-opaque marker such as gold. Needless to say, anyother radio-opaque markers may be provided on the stents.

Where the stents are made of a biodegradable material, such that it hasa limited lifespan, the stents remain in place until they dissolve.Anti-platelet therapy is frequently recommended for patients that havereceived a stent. In the case that the stents are biodegradable,anti-platelet medication can be discontinued after dissolution of thestent.

Where the stents are not biodegradable, they are left in place andprovide a scaffolding over which endothelial cells will grow over time.

The stents are deployed over a stenotic area (as described above). Anarrower central portion is located in the bore of the stenosis in orderto maintain or increase the diameter of the bore of the stenosis to anextent that restores blood flow distally. The diameter of the centralportion is sufficient to open the stenosis to restore blood flow but itdoes not open the stenosis fully, rather it achieves around 50% of thediameter of the healthy artery.

The relatively small diameter of the central portion of the stentsaccording to the invention acts to minimise the amount of material fromthe stenosis that is pushed into adjacent unoccupied areas of theartery. Furthermore, the sub-maximal angioplasty achieved by the stentsminimises the likelihood of fracturing the plaque of the stenosis, andtherefore minimises the chance of distal vessel stenosis.

Conventional self-expanding stents are anchored in place by the outwardforce of the stent on vessel walls along the whole length of the stent.This outward force causes a significant amount of atherosclerotic debristo be pushed to the walls of the blood vessel. Atherosclerotic debristhat is pushed against walls of the blood vessel can be forced intoadjacent side branches or small vessels (snow-ploughing). The arterialstructure in the brain is highly branched and the presence of many sidebranches can readily lead to snow-ploughing in the case wheresignificant amounts of atherosclerotic debris are forced againstarterial walls.

In use of the stents according to the invention, the two larger diameterfirst and second end portions bear against the arterial wall of theartery to stabilise and support the narrower central portion thefunction of which is to open the stenosis. The construction minimisesthe amount of plaque that is pushed along the arterial walls by thestents, since it is only the first and second end portions that contactthe arterial walls.

The central portion of the stents is constructed to exert a higheroutward radial force than that exerted by the first and second endportions.

As discussed above, the provision of the central portion and thetransition portions of the stents according to the invention beingformed with relatively small interstices, minimises, and in general,prevents material from the stenosis being forced through the intersticesin the central portion and the transition portions of the stentsaccording to the invention. If material from the stenosis is forcedthrough the interstices of the stents, small particles of plaque can bereleased from the stents back into the blood vessel; this is theso-called “cheese-grating” effect. These small plaque particles canfloat into the distal circulation, moving deeper into the brainvasculature, potentially causing distal emboli. By minimising the areaof the interstices in the central and transition portions of the stentsaccording to the invention, the “cheese-grating” effect is minimised.

Similarly, a dual layer construction for the stents according to theinvention can be used to further decrease the “cheese-grating” effect ofatherosclerotic plaque.

A biocompatible film or membrane can be provided to a surface of thestents, to further reduce the incidence of the “cheese-grating” effect,thereby minimising the release of distal emboli into the intracranialcirculation.

The stents of the present invention provide an early stage, non-medicaltreatment for ICAS and reduce the complications associated withconventional stent treatments of ICAS by, for example, minimising plaqueforced into interstices of the stent (‘cheese-grating’), reducing theplaque pushed into arterial side branches by the stent (snow-ploughing),reducing the risk of intracranial hyperperfusion injury, providing lowshear stress so as to reduce the occurrence of restenosis, andminimising plaque occluding the stent, ultimately reducing morbidity andmortality.

It is also envisaged that the stents according to the invention maycomprise a composite structure, for example, Drawn Filled Tube Nitinol(DFT).

It is also envisaged that the stents according to the invention may becoated with graphene.

While the stents according to the invention have been described andillustrated with the axial length of the first and second walls of thefirst and second end portions being of equal length, it is envisagedthat in some embodiments of the invention the axial length of the firstand second walls of the first and second end portions of the stents maybe different. For example, it is envisaged that the first walls of thefirst end portions, which would be located at the proximal end of thestenosis may be of axial length shorter than the axial length of thesecond wall of the second end portion. Alternatively, the axial lengthof the second wall of the second end portion of the stent may be ofaxial length shorter than the axial length of the first wall of thefirst end portion of the stent. In general, in cases where a perforatorvessel is located relatively close to either the proximal or distal endof the stenosis, the axial length of the first or second wall of thefirst or second end portion, as the case may be of the stent may beshorter than the axial length of the other one of the first and secondwalls of the first and second end portions of the stent, in order toengage the non-diseased part of the artery adjacent the stenosis betweenthe stenosis and the perforator vessel without blocking or covering theperforator vessel. For example, in the case of a perforator vessel beingrelatively close to a stenosis on the distal end of the stenosis, thesecond wall of the second end portion of the stent would be of axiallength shorter than the axial length of the first wall of the first endportion of the stent, and the axial length of the second wall of thesecond end portion would be such that the second end portion of thestent would engage the non-diseased part of the artery adjacent thestenosis and between the stenosis and the adjacent perforator vessel.

Therefore, it is envisaged that the axial length of the first and secondwalls of the first and second end portions of the stents according tothe invention may be the same or different.

Additionally, it will be appreciated that the external and internaldiameters of the first and second end portions may be different. Forexample, in a case where the diameters of the vessel at the respectiveopposite ends of the stenosis are different, the diameters of the firstand second end portions would be appropriately selected.

It is also envisaged that the stent 70 described with reference to FIG.12 when being positioned in the stenosis, instead of the second endportion 4 of the stent being located distally of the perforator 109, thestent may be urged proximally in order to locate the second end portion4 of the stent between the stenosis and the perforator 109. It isfurther envisaged that in cases where a perforator 109 is branched froman artery or vessel adjacent a stenosis, either on the proximal ordistal end of the stenosis, and there is no space between the stenosisand the branched perforator vessel, it is envisaged that the adjacentone of the first and second end portions of the stent may be located toextend over the perforator vessel 19, and a blood supply would beaccommodated through the interstices 20 b through the corresponding oneof the first and second walls of the relevant one of the first andsecond end portions 3 or 4 of the stent into the perforator vessel 103.

The invention claimed is:
 1. An intracranial stent having an expandedstate and an unexpanded state, the intracranial stent comprising: afirst end portion defining a first bore; a second end portion spacedapart from the first end portion and defining a second bore; a centralportion extending between the first and second end portions and defininga central bore, the central bore being in communication with the firstand second bores, the central portion having an external diameter thatis smaller than respective external diameters of the first and secondend portions when the intracranial stent is in the expanded state, theexternal diameter of the central portion being 1 mm to 3 mm and theexternal diameters of the first and second end portions each being 2 mmto 5 mm, an entire axial length of the intracranial stent being definedby the first end portion, the second end portion, the central portion,and a pair of transition portions connecting the first end portion tothe central portion and connecting the second end portion to the centralportion; and a repeating pattern of interstices formed in the first endportion, in the second end portion, and in the central portion, each ofthe interstices in the central portion being smaller than each of theinterstices in the first end portion and in the second end portion, theinterstices in the central portion each forming a “V” angle that islarger in the expanded state as compared to the unexpanded state, the“V” angle being greater than 40 degrees in the expanded state and lessthan 5 degrees in the unexpanded state, wherein the first and second endportions are sized to engage an arterial wall of an intracranial vesselwhen the intracranial stent is in the expanded state, and the centralportion, the first end portion, and the second end portion are sized topass within a bore of a stenosis in the intracranial vessel when theintracranial stent is in the unexpanded state.
 2. The intracranial stentof claim 1, wherein the intracranial stent has an external diameter of0.6 mm or less, in the unexpanded state, to facilitate positioning ofthe central portion within the bore of the stenosis.
 3. The intracranialstent of claim 1, wherein the central portion is defined by an outerwall that is sized to bear solely on stenotic material and not on a wallof the intracranial vessel, the first end portion and the second endportion defining respective cylindrical outer walls that are connectedto the central portion by a pair of curved transition walls, when theintracranial stent is in the expanded state.
 4. The intracranial stentof claim 1, wherein an axial length of the central portion is 5 mm to 20mm, an axial length of the first end portion is 2 mm to 3 mm, and anaxial length of the second end portion is 2 mm to 3 mm, such that, whenthe intracranial stent is in the expanded state, the first and secondend portions are configured to engage the wall of the intracranialvessel at positions that are adjacent to respective opposite ends of thestenosis.
 5. The intracranial stent of claim 1, wherein, when theintracranial stent is in the expanded state, the central portion of theintracranial stent is configured to bear on stenotic material with aforce sufficient to increase or retain a diameter of the bore of thestenosis to maintain or increase a rate of blood flow through thestenosis.
 6. The intracranial stent of claim 1, further including firstand second transition portions that respectively connect the first endportion and the second end portion to the central portion, the firsttransition portion and the second transition portions being angled suchthat the first transition portion and the second transition portion eachdefine a taper in a direction towards the central portion, the taperseach beginning at one of the first end portion and the second endportion and ending at the central portion, the first transition portionand the second transition portion being configured to contact a portionof the stenosis in the intracranial vessel when the intracranial stentis in the expanded state.
 7. The intracranial stent of claim 1, whereinthe external diameters of the first and second end portions, when theintracranial stent is in the expanded state, are each 100%-125% of adiameter of the intracranial vessel.
 8. The intracranial stent of claim1, wherein the central portion has a maximum expanded diameter that issmaller than a diameter of a non-diseased portion of the intracranialvessel.
 9. The intracranial stent of claim 1, wherein the intracranialstent is coated with an angiogenesis promoting material, aplaque-inhibiting material, or both.
 10. An expandable intracranialstent, comprising: an expandable proximal portion having a proximalopening and a narrower transition opening; an expandable distal portionhaving a distal opening and a narrower transition opening; an expandablecentral portion extending between the transition openings of theproximal and distal portions; a pair of transition portions that connectthe proximal portion and the distal portion, respectively, to thecentral portion via the transition openings; and a repeating pattern ofinterstices being formed in the proximal portion, in the distal portion,and in the central portion, each of the interstices in the centralportion being smaller than respective interstices in the proximalportion and in the distal portion, the interstices in the centralportion each forming a “V” angle that is larger in the expanded state ascompared to the unexpanded state, the “V” angle being greater than 40degrees in the expanded state and less than 5 degrees in the unexpandedstate, the central portion having an axial length that is longer than acombined axial length of one transition portion and the proximal portionor longer than a combined axial length of another transition portion andthe distal portion, the intracranial stent being expandable from anunexpanded state in which respective external diameters of the proximalportion, distal portion, and central portion are all reduced, ascompared to the external diameters of the proximal portion, the distalportion, and the central portion, when the intracranial stent is in anexpanded state in which the proximal portion and the distal portion forma widest external diameter of the intracranial stent of 2 mm to 5 mm,and in which the central portion reduces in external diameter from theexternal diameters of the proximal portion and the distal portion to anexternal diameter of 1 mm to 3 mm.
 11. The intracranial stent of claim10, wherein the external diameters of the proximal portion, distalportion, and central portion are approximately equal when theintracranial stent is in the unexpanded state.
 12. The intracranialstent of claim 10, wherein the proximal portion and the distal portionhave cylindrical shapes, the external diameters of the proximal portionand distal portion are approximately equal to each other along thecylindrical shapes of the proximal portion and the distal portion whenthe intracranial stent is in the expanded state.
 13. An intracranialstent having an expanded state and an unexpanded state, the intracranialstent comprising: a first end portion having a first bore extendingtherethrough; a second end portion spaced apart from the first endportion and having a second bore extending therethrough; a centralportion extending between the first and second end portions and having acentral bore extending therethrough, the central bore being incommunication with the first and second bores, the central portionhaving an external diameter of 1 mm to 3 mm, the external diameter ofthe central portion being smaller than respective external diameters ofthe first and second end portions when the intracranial stent is in theexpanded state; and a repeating pattern of interstices being formed inthe first end portion, in the second end portion, and in the centralportion, each of the interstices in the central portion being smallerthan respective interstices in the first end portion and in the secondend portion, the interstices in the central portion each forming a “V”angle that is larger in the expanded state as compared to the unexpandedstate, the “V” angle being greater than 40 degrees in the expanded stateand less than 5 degrees in the unexpanded state, wherein the first andsecond end portions are sized to engage an arterial wall of anintracranial vessel when the intracranial stent is in the expanded statedue to an expanded external diameter of the first and second endportions being 2 mm to 5 mm, the central portion and first and secondend portions having an unexpanded external diameter of 0.6 mm or less inthe unexpanded state, an axial length of the central portion being 5 mmto 20 mm and axial lengths of the first end portion and the second endportion being 2 mm to 4 mm, the axial length of the central portionbeing longer than a combined axial length of one transition portion andthe first end portion or longer than a combined axial length of anothertransition portion and the second end portion.
 14. The intracranialstent of claim 13, wherein the expansion of the intracranial stent isconfigured to generate force sufficient to enlarge a bore withinstenotic material within an intracranial vessel and thereby increase aflow of blood through the intracranial vessel.
 15. The intracranialstent of claim 13, wherein the external diameter of the central portionis 25% to 70% of the external diameters of the first and second endportions when the intracranial stent is in the expanded state.
 16. Theintracranial stent of claim 13, wherein the unexpanded external diameteralong an entire axial length of the intracranial stent is 0.6 mm orless.
 17. The intracranial stent of claim 1, wherein the intracranialstent is configured, when in the expanded state, to form an annuluswithin which stenotic material is retained.
 18. The intracranial stentof claim 1, wherein the central portion is configured, with theintracranial stent in the expanded state, to expand to a size where theexternal diameter of the central portion is in the range of 25% to 80%of a diameter of a non-diseased part of the intracranial vessel adjacenta proximal or a distal end of the stenosis.
 19. The intracranial stentof claim 1, wherein the central portion is configured, with theintracranial stent in the expanded state, to increase the diameter ofthe bore formed by the stenosis to increase the rate of blood flowflowing to an intracranial site through the stenosis to lie in the rangeof 25% to 80% of normal blood flow rate through the vessel without thestenosis, in order to promote a natural intracranial angiogenesisprocess at the intracranial site.
 20. The intracranial stent of claim19, wherein the central portion is configured, with the intracranialstent in the expanded state, to increase the diameter of the bore formedby the stenosis to increase the rate of the blood flow flowing throughthe stenosis to approximately 50% of the normal blood flow rate throughthe vessel without the stenosis.
 21. The intracranial stent of claim 1,wherein the central portion is configured, with the intracranial stentin the expanded state, to apply a radial outward pressure to thestenosis so that squashing of material forming the stenosis is minimizedto thereby minimize urging the material forming the stenosislongitudinally along the wall of the vessel.
 22. The intracranial stentof claim 1, wherein the first and second end portions are configured,with the intracranial stent in the expanded state, to bear on the wallof the vessel with a pressure sufficient to prevent material forming thestenosis being urged between the corresponding one of the first andsecond end portions and the wall of the vessel.
 23. The intracranialstent of claim 6, wherein the transition portions each have afrusto-conical shape, including the respective taper, when theintracranial stent is in the expanded state.
 24. The intracranial stentof claim 9, wherein the angiogenesis promoting material comprisesmethacrylic acid-co-isodecyl acrylate.
 25. The intracranial stent ofclaim 1, wherein the first and second end portions in the expanded stateof the stent have cylindrical outer walls that match respective shapesof the first bore and of the second bore.
 26. An intracranial stent,comprising: a proximal end portion having a proximal opening; a distalend portion having a distal opening; a central portion extending betweenthe proximal and distal end portions; and a repeating pattern ofinterstices formed in the proximal end portion, in the distal endportion, and in the central portion, each of the interstices in thecentral portion being smaller than respective interstices in theproximal end portion and in the distal end portion; the intracranialstent having an unexpanded state in which: a maximum external diameterof the intracranial stent is 0.6 mm or less, and the maximum externaldiameter is constant along an entire length of the intracranial stentextending from the proximal opening to the distal opening, and theintracranial stent being self-expandable to an expanded state in which:the maximum external diameter of the intracranial stent increases from0.6 mm or less to 2 mm to 5 mm, the maximum external diameter beingpresent at the proximal end portion or at the distal end portion, and anexternal diameter of the central portion increases from 0.6 mm or lessto an external diameter that is less than the maximum external diameterof the intracranial stent in the expanded state, the external diameterof the central portion being 1 mm to 3 mm, wherein the interstices inthe central portion each form a “V” angle that is larger in the expandedstate as compared to the unexpanded state, the “V” angle being greaterthan 40 degrees in the expanded state and less than 5 degrees in theunexpanded state.
 27. The intracranial stent of claim 1, wherein theinterstices in the central portion extend, in a repeating manner, aroundan entirety of the central portion.
 28. An expandable intracranialstent, comprising: a proximal portion having a proximal opening and anarrower transition opening; a distal portion having a distal openingand a narrower transition opening; a central portion extending betweenthe transition openings of the proximal and distal portions; a pair oftransition portions that connect the proximal portion and the distalportion, respectively, to the central portion via the transitionopenings; and interstices formed in the proximal portion, in the distalportion, and in the central portion, the interstices in the centralportion each forming a “V” angle that is larger in the expanded state ascompared to the unexpanded state, the “V” angle being greater than 40degrees in the expanded state and less than 5 degrees in the unexpandedstate, the central portion having an axial length that is longer than acombined axial length of one transition portion and the proximal portionor longer than a combined axial length of another transition portion andthe distal portion, the intracranial stent being expandable from anunexpanded state in which respective external diameters of the proximalportion, distal portion, and central portion are all reduced, ascompared to the external diameters of the proximal portion, the distalportion, and the central portion, when the intracranial stent is in anexpanded state, and the proximal portion and the distal portion, in theexpanded state, forming a widest external diameter of the intracranialstent of 2 mm to 5 mm, and the central portion reducing in externaldiameter from the external diameters of the proximal portion and thedistal portion to an external diameter of 1 mm to 3 mm.